Methods and devices for skin tightening

ABSTRACT

The present invention relates to methods and devices for skin tightening after incising or excising tissue portions from a subject. Exemplary methods and devices include tunable dressings having an adhesive layer and a regulatable layer or an un-stretched layer that responds to one or more external stimuli to contract or expand the dressing, where the contraction or expansion can be uniform or non-uniform.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 14/764,866, filed on Jul. 30, 2015, which is a U.S. National PhaseApplication under 35 U.S.C. § 371 of International Patent ApplicationNo. PCT/US2014/016483, filed on Feb. 14, 2014, which claims benefit ofU.S. Provisional Application No. 61/766,937, filed Feb. 20, 2013, thecontents of each of which are hereby incorporated by reference in theirentirety.

BACKGROUND OF THE INVENTION

This invention relates to methods and devices for skin tightening or fortreating diseases, disorders, and conditions that would benefit fromskin restoration or tightening.

Many human health issues arise from the damage or loss of tissue due todisease, advanced age, and/or injury. In aesthetic medicine, eliminationof excess tissue and/or skin laxity is an important concern that affectsmore than 25% of the U.S. population. Conventional surgical therapies(e.g., a face lift, brow lift, or breast lift) can be effective but areoften invasive, inconvenient, and expensive, while scarring limits itsapplicability.

Although minimally invasive methods are available, such methods aregenerally less effective than surgical methods. Methods using energysources (e.g., laser, non-coherent light, radiofrequency, or ultrasound)can be effective at improving the architecture and the texture of theskin but are much less effective at tightening the skin or reducing skinlaxity. Neurotoxins, such as botulinum toxin, reduce the formation ofdynamic wrinkles by paralysis of the injected muscles, but such toxinshave minimal or no effect on skin tightness or laxity. Finally, dermalfillers, such as hyaluronic acid, are injected in the dermal layer tosmooth out wrinkles and improve contours, but such fillers do nottighten or reduce laxity of the skin. Thus, surgical therapies remainthe gold standard for lifting and/or tightening skin, as compared toenergy-based techniques (e.g., with laser, radiofrequency, or ultrasoundablation) and injection-based techniques (e.g., with botulinum toxin orhyaluronic acid- or collagen-based fillers).

Accordingly, there is a need for improved methods and devices thatincrease the effectiveness of minimally-invasive techniques whilemaintaining convenience, affordability, and/or accessibility to patientsrequiring tissue restoration.

SUMMARY OF THE INVENTION

This invention relates to methods and devices (e.g., a dressing) for thetightening of skin (or the reduction of skin laxity) by selectiveopening or closing a plurality of small slits or holes (e.g., wounds)formed by incision or excision of tissue portions. For example, tissueexcision can be performed by fractional ablation of the epidermal and/ordermal layer of the skin with a hollow coring needle, by fractionallaser ablation, by fractional radiofrequency ablation, or by fractionalultrasonic ablation. Various methods and devices are provided to closesmall wounds, including smart or tunable dressings that allow fortitration of the tightening effect after application to the skin of asubject.

Accordingly, the present invention features a tunable dressing including(i) an adhesive layer and (ii) a regulatable layer that includes one ormore materials, where exposure of the regulatable layer to one or moreexternal stimuli (e.g., any described herein) results in a change in aphysical characteristic (e.g., any described herein) in the one or morematerials in at least a portion of the dressing (e.g., including planaror non-planar changes across the entire device or in a portion of thedevice).

The present invention also features a tunable dressing including (i) anadhesive layer and (ii) an unstretched layer that includes one or morematerials, where exposure of the unstretched layer to one or moreexternal stimuli (e.g., any described herein) results in contraction orexpansion in one or more directions (e.g., in the x-, y-, z-, xy-, xz-,yz-, and/or xyz-directions) in at least a portion of the area of thedressing. In some embodiments, the contraction or expansion is in thex-axis, y-axis, and/or z-axis of the dressing, as compared to before theexposure (e.g., in the xy-, xz-, yz-, and/or xyz-plane of the dressing,as compared to before the exposure). In further embodiments, thecontraction or expansion is uniform or non-uniform.

In some embodiments, the change in a physical characteristic includes anincrease in tension of the dressing, a decrease in tension of thedressing, an increase in compressive force exerted by the dressing, adecrease in compressive force exerted by the dressing, compression inone or more directions of the dressing, and/or expansion in one or moredirections of the dressing (e.g., where such an increase or decrease isin the x-axis, y-axis, and/or z-axis or in the xy-, xz-, xy-, and/orxyz-plane of the dressing, as compared to before the exposure). Inparticular embodiments, the increase or decrease in tension orcompressive force and/or the expansion or compression of the device isan increase or decrease of intensity of at least about 0.5% afterexposure of the one or more external stimuli, as compared to before theexposure (e.g., an increase or decrease of at least about 0.5% (e.g., atleast about 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.5%, 1.7%, 2.0%,2.2%, 2.5%, 2.7%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%,8.5%, 9%, 9.5%, 10%, 10.5%, 15%, 20%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,or more) or from about 0.5% to 20%, 20% to 30%, 30% to 40%, 30% to 50%,or 50% to 60%). In some embodiments, the physical characteristic is oneor more of compression, expansion, tension, structure, size, porosity,surface chemistry, bending modulus, fracture or failure strain,resilience, permeability, swelling ratio, elasticity, electricconductivity, plasticity, resilience, resistance (e.g., creepresistance), strength (e.g., as measured by Young's modulus, tensilestrength, compressive strength, impact strength, or yield strength),stress (e.g., compressive stress, shear stress, or tensile stress),load, and/or strain (e.g., as measured by deflection, deformation,strain at failure, or ultimate strain).

In any embodiment described herein, the change in a physicalcharacteristic occurs in a portion of the dressing or across the entiredressing. In other embodiments, the change in a physical characteristicis non-uniform across the entire dressing or in a portion of thedressing. In yet other embodiments, the change in a physicalcharacteristic is uniform across the entire dressing or in a portion ofthe dressing.

In any of the devices, dressings, apparatuses, and methods describedherein, the one or more materials are configured in a random,non-geometric, and/or geometric arrangement to provide contractionand/or expansion in one or more directions in at least a portion of thearea of the dressing. In particular embodiments, the arrangement isgeometric (e.g., a uniform or non-uniform arrangement). In someembodiments, the geometric arrangement includes a first materialarranged in a first direction and optionally a second material arrangedin a second direction (e.g., where the second direction is approximatelyorthogonal to the first direction). In further embodiments, each of thefirst material or the second material is, independently, a shape-memorypolymer, a shape-memory alloy, a thermal-responsive material, apH-responsive material, a light-responsive material, amoisture-responsive material, a solvent-responsive or chemicalexposure-responsive material, an electric field-responsive material, amagnetic field-responsive material, an actuator-embedded material, or anunstretched material (e.g., any described herein).

In any of the devices, dressings, apparatuses, and methods describedherein, the one or more external stimuli is, independently, a change intemperature, pH, light, moisture, solvent, chemical exposure, electricfield, and/or magnetic field (e.g., which can optionally result inmechanical, hydraulic, and/or pneumatic tuning).

In any embodiment described herein, exposure of the device (e.g.,dressing or a layer of the device, as well as portions thereof) to twoor more external stimuli (e.g., three, four, five, six, seven, eight,nine, ten, or more external stimuli) results in a change in two or morephysical characteristics (e.g., three, four, five, six, seven, eight,nine, ten, or more changes in physical characteristics).

In any embodiment described herein, the regulatable layer or theunstretched layer includes two or more materials (e.g., three, four,five, six, seven, eight, nine, ten, or more materials). In particularembodiments, at least one of the materials (e.g., at least two, three,four, five, or more in one, two, three, four, or more layers) is astimulus-responsive material (e.g., any described herein). Exemplarymaterials include a shape-memory polymer (e.g., including shape-memorypolyurethane; block copolymers including poly(ethylene terephthalate),polystyrene, polyethylene glycol, poly(1,4-butadiene), polynorbornene,polyacrylate, and/or polyurethane, as well as shape-memory compositesand shape-memory hybrids), a shape-memory alloy (e.g., any alloydescribed herein, such as a NiTi alloy), a thermal-responsive material(e.g., any such material described herein, such as polymers includingpoly-N-isopropylacrylam ide, poly-N-vinylcaprolactam,poly-N,N-diethylacrylamide, and/or a polyalkylacrylamide), apH-responsive material (e.g., any described herein, such as polymers andcopolymers including one or more polyacrylic acid, polymethacrylic acid,methacrylic acid/methyl methacrylate, and carboxylic derivatives of anymonomer described herein), a light-responsive material (e.g., a polymerincluding one or more light-responsive switches, as described herein), amoisture-responsive material (e.g., a polymer including one or moreionic monomers, as described herein), a solvent-responsive or chemicalexposure-responsive material (e.g., a polymer composite, as describedherein), an electric field-responsive material (e.g., a polymerincluding one or more electric field-responsive switches, as describedherein), a magnetic field-responsive material (e.g., a polymer includingone or more magnetic field-responsive switches, as described herein), anactuator-embedded material (e.g., a material including one or more MEMSactuators, carbon nanotubes, piezoceramic actuators (e.g., optionallyhaving one or more interdigitated electrodes), multilayered actuators,optical fibers, piezopolymeric films, piezoplates, piezofibers,shape-memory polymers, or shape-memory alloys). In other embodiments, atleast one of the materials (e.g., at least two, three, four, five, ormore in one, two, three, four, or more layers) is a conventionalmaterial and/or a rigid material (e.g., any described herein, such asalginate, benzyl hyaluronate, carboxymethylcellulose, cellulose acetate,chitosan, collagen, dextran, epoxy, gelatin, hyaluronic acid,hydrocolloids, nylon (e.g., nylon 6 or PA6), pectin, poly (3-hydroxylbutyrate-co-poly (3-hydroxyl valerate), polyacrylate (PA),polyacrylonitrile (PAN), polybenzimidazole (PBI), polycarbonate (PC),polycaprolactone (PCL), polyester (PE), polyethylene glycol (PEG),polyethylene oxide (PEO), PEO/polycarbonate/polyurethane (PEO/PC/PU),poly(ethylene-co-vinyl acetate) (PEVA), PEVA/polylactic acid (PEVA/PLA),poly (ethylene terephthalate) (PET), PET/poly (ethylene naphthalate)(PET/PEN) polyglactin, polyglycolic acid (PGA), polyglycolicacid/polylactic acid (PGA/PLA), polyimide (PI), polylactic acid (PLA),poly-L-lactide (PLLA), PLLA/PC/polyvinylcarbazole (PLLA/PC/PVCB), poly((3-malic acid)-copolymers (PMLA), polymethacrylate (PMA), poly (methylmethacrylate) (PMMA), polystyrene (PS), polyurethane (PU), poly (vinylalcohol) (PVA), polyvinylcarbazole (PVCB), polyvinyl chloride (PVC),polyvinylidenedifluoride (PVDF), polyvinylpyrrolidone (PVP), silicone,rayon, or combinations thereof).

In any embodiment described herein, the dressing is tunable withoutremoval of a portion of the dressing (e.g., without removal of one ormore layers of the dressing). In any embodiment described herein, theadhesive layer includes a continuous layer of one or more adhesivematerials or a discontinuous layer of one or more adhesive materials. Infurther embodiments, the discontinuous layer includes one or moreadhesive materials in a random, geometric, or non-geometric arrangement(e.g., an array of one or more adhesive materials). In particularembodiments, the adhesive layer is tunable (e.g., results in a change ina physical characteristic in the one or more adhesive materials in atleast a portion of the dressing or across the entire dressing).Exemplary adhesive materials include any described herein, such as abiodegradable adhesive; a pressure sensitive adhesive (e.g., a naturalrubber, synthetic rubber (e.g., a styrene-butadiene or styrene-ethylenecopolymer), polyvinyl ether, polyurethane, acrylic, silicone, or aethylene-vinyl acetate copolymer); a biocompatible matrix (e.g.,collagen (e.g., a collagen sponge), low melting agarose (LMA),polylactic acid (PLA), and/or hyaluronic acid (e.g., hyaluranon)); aphotosensitizer (e.g., Rose Bengal, riboflavin-5-phosphate (R-5-P),methylene blue (MB), N-hydroxypyridine-2-(1H)-thione (N-HTP), aporphyrin, or a chlorin, as well as precursors thereof); a photochemicalagent (e.g., 1,8 naphthalimide); a synthetic glue (e.g., a cyanoacrylateadhesive, a polyethylene glycol adhesive, or agelatin-resorcinol-formaldehyde adhesive); or a biologic sealant (e.g.,a mixture of riboflavin-5-phosphate and fibrinogen, a fibrin-basedsealant, an albumin-based sealant, or a starch-based sealant).

In any embodiment described herein, the devices, apparatuses, dressings,and/or methods include one or more therapeutic agents selected fromgrowth factors, analgesics (e.g., an NSAID, a COX-2 inhibitor, anopioid, a glucocorticoid agent, a steroid, or a mineralocorticoid agent,or any described herein), antibiotics, antifungals, anti-inflammatoryagents, antimicrobials (e.g., chlorhexidine-, iodine-, or silver-basedagents, as described herein), antiseptics (e.g., an alcohol, aquaternary ammonium compound, or any described herein),antiproliferative agents, steroids (for example, steroids to preventedema), agents which prevent post-inflammatory skin hyperpigmentation(e.g., hydroquinone, azelaic acid, kojic acid, mandelic acid, orniacinamide), emollients, hemostatic agents, procoagulative agents,anticoagulative agents, immune modulators, proteins, or vitamins. Inparticular embodiments, the therapeutic agent is a hemostatic agent, aprocoagulative agent, an anticoagulative agent, or combinations thereof.In some embodiments, the therapeutic agent is selected from the group ofanhydrous aluminum sulfate, anti-fibrinolytic agent(s) (e.g., epsilonaminocaproic acid, tranexamic acid, or the like), anti-platelet agent(s)(e.g., aspirin, dipyridamole, ticlopidine, clopidogrel, or prasugrel),calcium alginate, cellulose, chitosan, coagulation factor(s) (e.g., II,V, VII, VIII, IX, X, XI, XIII, or Von Willebrand factor, as well asactivated forms thereof), collagen (e.g., microfibrillar collagen),coumarin derivative(s) or vitamin K antagonist(s) (e.g., warfarin(coumadin), acenocoumarol, atromentin, phenindione, or phenprocoumon),desmopressin, epinephrine, factor Xa inhibitor(s) (e.g., apixaban orrivaroxaban), fibrinogen, heparin or derivatives thereof (e.g., lowmolecular weight heparin, fondaparinux, or idraparinux), poly-N-acetylglucosamine, potassium alum, propyl gallate, silver nitrate, thrombin,thrombin inhibitor(s) (e.g., argatroban, bivalirudin, dabigatran,hirudin, lepirudin, or ximelagatran), titanium oxide, or a zeolite(e.g., a calcium-loaded zeolite).

The tunable dressings of the invention may also include moisturizers,emollients, ointments (including occlusive ointments and non-occlusiveointments), lotions, or creams, which may, if desired, provide a liquidor vapor barrier. Ingredients typically found in these materials includepetrolatum, lanolin, glycerin, panthenol, paraffin, microcrystallinewax, ceresine, wool fat, bees wax, emulsifying wax, ceremide, andvegetable oils (e.g., olive, peanut, or coconut oil).

The present invention features a kit including: (a) a tunable dressing(e.g., any described herein) and (b) an applicator, where the applicatoris configured for positioning the dressing on a skin region. In someembodiments, the applicator includes a frame or any structure configuredto affix a dressing to the skin region (e.g., a disposable frame or adisposable structure). In some embodiments, the applicator holds thedressing to allow for aligning, positioning, and/or placing the dressingon the desired skin region. In yet other embodiments, the applicator isconfigured to allow for affixing a tunable dressing immediately after orshortly after forming one or more incisions or excisions in the skinregion (e.g., within about 30 seconds, as described herein). In otherembodiments, the kit includes a mechanical ablation device.

The present invention also features a kit including: (a) a tunabledressing (e.g., any described herein) and (b) an apparatus for makingincisions and/or excisions in a skin region (e.g., a microablation tool,such as a fractional laser microablation tool, a fractionalradiofrequency microablation tool, or a fractional ultrasonicmicroablation tool). In some embodiments, the kit further includes anapplicator (e.g., any described herein), where the applicator isstructurally configured to attach to the apparatus for making one ormore incisions and/or excisions and to release a device (e.g., a tunabledressing) after making such an incision or excision.

In further embodiments, any of the kits described herein can include oneor more of instructions on how to use the device(s), an air blower, askin cooling device (e.g., cold air blower, Zimmer cooler, cold plate orother cold surface applied to the skin, cold gas, or cold liquid), aheat gun, a heating pad, one or more therapeutic agents (e.g., anydescribed herein, such as an anticoagulative and/or procoagulativeagent, and optionally in combination with a useful dispenser forapplying the therapeutic agent, such as a brush, spray, film, ointment,cream, lotion, or gel), one or more wound cleansers (e.g., including anyantibiotic, antimicrobial, or antiseptic, such as those describedherein, in any useful form, such as a brush, spray, film, ointment,cream, lotion, or gel), one or more debriding agents, and/or othersuitable or useful materials.

The present invention features methods of skin tightening including: (i)affixing a device to a skin region, where the skin region includes aplurality of incised tissue portions and/or excised tissue portions (forexample, where at least two of the tissue portions have an arealdimension that is less than about 1 mm² and/or where at least two of thetissue portions has a dimension that is less than about 1 mm), and wherethe device provides contraction or expansion of the skin region in oneor more directions; and (ii) adjusting the contraction or expansion byexposing the affixed device to one or more external stimuli that resultin a change in a physical characteristic of the affixed device. In someembodiments, the areal dimension is less than or equal to about 1.0 mm²(e.g., less than or equal to about 0.9 mm², 0.8 mm², 0.7 mm², 0.6 mm²,0.5 mm², 0.4 mm², 0.3 mm², 0.2 mm², 0.1 mm², 0.07 mm², 0.05 mm², 0.03mm², 0.02 mm², 0.01 mm², 0.007 mm², 0.005 mm², 0.003 mm², 0.002 mm², or0.001 mm²) or between about 0.001 mm² and 1.0 mm² (e.g., as describedherein).

In some embodiments, the skin region or treated skin region includes aplurality of incised tissue portions and/or excised tissue portions(e.g., a plurality of holes and/or slits). In some embodiments, at leastone (e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45,50, 75, 100, or more tissue portions, such as between about 2 and 100tissue portions, as described herein) of the tissue portions has atleast one dimension that is less than about 2.0 mm (e.g., less than orequal to about 1.5 mm, 1 mm, 0.75 mm, 0.5 mm, 0.3 mm, 0.2 mm, 0.1 mm,0.075 mm, 0.05 mm, or 0.025 mm) or between about 0.025 mm and 2.0 mm(e.g., as described herein). In some embodiments, the plurality ofincised tissue portions and/or excised tissue portions include one ormore elliptical holes in the skin region. In other embodiments, theplurality of incised tissue portions and/or excised tissue portionsincludes any useful shape (e.g., a cylinder, hole, slit, elongatedstrip, or other geometries). In further embodiments, the areal fractionof the skin region to be removed is less than about 70% (e.g., less thanabout 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 10%, or 5%) orbetween about 5% and 80% (e.g., as described herein). In someembodiments, the plurality of tissue portions are incised or excised inany beneficial pattern within the skin region (e.g., as describedherein).

In some embodiments, affixing step (i) is performed within about 30seconds of incising and/or excising the skin region (e.g., within about20, 15, 10, 5, 3 seconds or less after forming an incision or excision).In other embodiments, the adjusting step (ii) provides selectivelyclosing or opening the incised tissue portions and/or excised tissueportions. In yet other embodiments, adjusting step (ii) includesadjusting the contraction or expansion across the entire device or aportion of the device. In further embodiments, the method results incontrolling pleating in the skin region.

In any embodiment described herein, the devices, dressings, apparatuses,and methods are useful for treating one or more diseases, disorders, orconditions to improve skin appearance, to rejuvenate skin, and/or totighten skin. Exemplary diseases, disorders, or conditions are describedherein and include removal of pigment, tattoo removal, veins (e.g.,spider veins or reticular veins), and/or vessels in the skin, as well astreatment of acne, allodynia, blemishes, ectopic dermatitis,hyperpigmentation, hyperplasia (e.g., lentigo or keratosis), loss oftranslucency, loss of elasticity, melasma (e.g., epidermal, dermal, ormixed subtypes), photodamage, rashes (e.g., erythematous, macular,papular, and/or bullous conditions), psoriasis, rhytides (or wrinkles,e.g., crow's feet, age-related rhytides, sun-related rhytides, orheredity-related rhytides), sallow color, scar contracture (e.g.,relaxation of scar tissue), scarring (e.g., due to acne, surgery, orother trauma), skin aging, skin contraction (e.g., excessive tension inthe skin), skin irritation/sensitivity, skin laxity (e.g., loose orsagging skin or other skin irregularities), striae (or stretch marks),vascular lesions (e.g., angioma, erythema, hemangioma, papule, port winestain, rosacea, reticular vein, or telangiectasia), or any otherunwanted skin irregularities.

Definitions

By “about” is meant +/−10% of any recited value.

By “incised” tissue portion or “incision” is meant a cut, abrasion, orablation of tissue, including a tissue portion in a skin region, or theact of cutting, abrading, destroying, or ablating tissue, a skin region,or one or more tissue portions. For example, an incision includes anycut, abrasion, or ablation into tissue, which can result in destructionof tissue or a portion thereof and, thereby, produce one or more holesor slits in the skin region. Exemplary methods of forming incised tissueportions or incisions include use of one or more blades, one or moresolid needles, fractional laser ablation, fractional radiofrequencyablation, and/or fractional ultrasonic ablation, any useful tool forforming incisions, or any methods and apparatuses described herein.

By “excised” tissue portion or “excision” is meant a removed tissue,including a tissue portion from a skin region, or the act of removingtissue or one or more tissue portions from a skin region. For example,an excision includes any removed tissue or tissue portion from a skinregion, which can result in excised tissue portions having a particulargeometry (e.g., a cylindrical geometry) and produce one or more holes(i.e., negative space created by the removal of tissue) in the skinregion. Exemplary methods of forming excised tissue portions orexcisions include use of one or more hollow needles (optionally includeone or more notches, extensions, protrusions, and/or barbs), one or moremicroaugers, one or more microabraders, any useful tool for formingexcisions, or any methods and apparatuses described herein.

By “physical characteristic” is meant a physical property of a device(e.g., a dressing) or a material included in the device. Exemplaryphysical characteristics include compression (or compressive force),expansion, tension (e.g., as measured by tensile stress), structure,size, porosity, surface chemistry, bending modulus, fracture or failurestrain, resilience, permeability, swelling ratio, elasticity (e.g., asmeasured by ultimate modulus of elasticity from the end-portion ofstress-strain curves that is greater than 10 N/mm²), electricconductivity, plasticity, resilience, resistance (e.g., as measured bycreep resistance), strength (e.g., as measured by Young's modulus (e.g.,a Young's modulus that is greater than about 1×10⁵ N/m), tensilestrength (e.g., a tensile strength that is greater than about 2 N/mm²),compressive strength, impact strength, or yield strength), stress (e.g.,as measured by compressive stress, shear stress, or tensile stress),load, strain (e.g., as measured by deflection, deformation, strain atfailure, or ultimate strain (extension before rupture), e.g., greaterthan about 30% or from about 30% to 130%), and other parameters, as wellas any described herein.

By “pleating” or “skin pleating” is meant any distortion in skin tissue(e.g., in the epidermal and/or dermal layers) that results in puckeringand/or folding. An exemplary schematic of skin pleating is provided inFIG. 6.

By “tunable” is meant capable of being adjusted, modified, or altered inone or more physical characteristics in response to one or more externalstimuli. Any part of the device can be tunable. For instance, in adressing, the regulatable layer and/or adhesive layer is tunable. In onenon-limiting example, a tunable dressing is a dressing including atleast one layer, where the structure of the layer changes in response toan external stimulus, such as a change in temperature. In anothernon-limiting example, a tunable dressing is a dressing including atleast one material, where the structure of the material changes inresponse to an external stimulus. The change in one physicalcharacteristic (e.g., change in structure at the molecular, microscopic,or macroscopic level) can exert a change in another physicalcharacteristic (e.g., a change in compressive force or tension exertedby the dressing) in one or more directions (e.g., in the x-, y-, z-,xy-, xz-, yz-, and/or xyz-direction). In one non-limiting example, apolymeric material can be optimized to facilitate change in structure atthe molecular level by altering the structure of the polymer chain(e.g., alterations to the side chain, linker regions, and/or precursormonomers), the particular block of the polymer (e.g., alterations tolength, molecular weight, hydrophobicity, or hydrophilicity), or one ormore co-polymeric blocks (e.g., alterations to weight percentage ratiosor post-polymerization modifications). The extent of change can beeither an increase or a decrease in a physical characteristic, ascompared to before exposure of the stimulus. Such an increase ordecrease can be of any useful extent, e.g., an increase or decrease ofat least about 0.5% (e.g., at least about 0.6%, 0.7%, 0.8%, 0.9%, 1.0%,1.1%, 1.2%, 1.5%, 1.7%, 2.0%, 2.2%, 2.5%, 2.7%, 3%, 3.5%, 4%, 4.5%, 5%,5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 15%, 20%,3.5%, 0.5% to 3%, 0.5% to 2.7%, 0.5% to 2.5%, 0.5% to 2.2%, 0.5% to2.0%, 0.5% to 1.7, 0.5% to 1.5%, 0.5% to 1.2, 0.5% to 1.1%, 0.5% to1.0%, 0.5% to 0.9%, 0.5% to 0.8%, 0.5% to 0.7%, 0.5% to 0.6%, 0.7% to20%, 0.7% to 15%, 0.7% to 10.5%, 0.7% to 10%, 0.7% to 9.5%, 0.7% to 9%,0.7% to 8.5%, 0.7% to 8%, 0.7% to 7.5%, 0.7% to 7%, 0.7% to 6.5%, 0.7%to 6%, 0.7% to 5.5%, 0.7% to 5%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, ormore) or from about 0.5% to 20% (e.g., from about 0.5% to 15%, 0.5% to10.5%, 0.5% to 10%, 0.5% to 9.5%, 0.5% to 9%, 0.5% to 8.5%, 0.5% to 8%,0.5% to 7.5%, 0.5% to 7%, 0.5% to 6.5%, 0.5% to 6%, 0.5% to 5.5%, 0.5%to 5%, 0.5% to 4.5%, 0.5% to 4%, 0.5% to 0.7% to 4.5%, 0.7% to 4%, 0.7%to 3.5%, 0.7% to 3%, 0.7% to 2.7%, 0.7% to 2.5%, 0.7% to 2.2%, 0.7% to2.0%, 0.7% to 1.7%, 0.7% to 1.5%, 0.7% to 1.2%, 0.7% to 1.1%, 0.7% to1.0%, 07% to 0.9%, 0.7% to 0.8%, 1.0% to 20%, 1.0% to 15%, 1.0% to10.5%, 1.0% to 10%, 1.0% to 9.5%, 1.0% to 9%, 1.0% to 8.5%, 1.0% to 8%,1.0% to 7.5%, 1.0% to 7%, 1.0% to 6.5%, 1.0% to 6%, 1.0% to 5.5%, 1.0%to 5%, 1.0% to 4.5%, 1.0% to 4%, 1.0% to 3.5%, 1.0% to 3%, 1.0% to 2.7%,1.0% to 2.5%, 1.0% to 2.2%, 1.0% to 2.0%, 1.0% to 1.7%, 1.0% to 1.5%,1.0% to 1.2%, 1.0% to 1.1%, 1.5% to 20%, 1.5% to 15%, 1.5% to 10.5%,1.5% to 10%, 1.5% to 9.5%, 1.5% to 9%, 1.5% to 8.5%, 1.5% to 8%, 1.5% to7.5%, 1.5% to 7%, 1.5% to 6.5%, 1.5% to 6%, 1.5% to 5.5%, 1.5% to 5%,1.5% to 4.5%, 1.5% to 4%, 1.5% to 3.5%, 1.5% to 3%, 1.5% to 2.7%, 1.5%to 2.5%, 1.5% to 2.2%, 1.5% to 2.0%, 1.5% to 1.7%, 2.0% to 20%, 2.0% to15%, 2.0% to 10.5%, 2.0% to 10%, 2.0% to 9.5%, 2.0% to 9%, 2.0% to 8.5%,2.0% to 8%, 2.0% to 7.5%, 2.0% to 7%, 2.0% to 6.5%, 2.0% to 6%, 2.0% to5.5%, 2.0% to 5%, 2.0% to 4.5%, 2.0% to 4%, 2.0% to 3.5%, 2.0% to 3%,2.0% to 2.7%, 2.0% to 2.5%, 2.0% to 2.2%, 2.5% to 20%, 2.5% to 15%, 2.5%to 10.5%, 2.5% to 10%, 2.5% to 9.5%, 2.5% to 9%, 2.5% to 8.5%, 2.5% to8%, 2.5% to 7.5%, 2.5% to 7%, 2.5% to 6.5%, 2.5% to 6%, 2.5% to 5.5%,2.5% to 5%, 2.5% to 4.5%, 2.5% to 4%, 2.5% to 3.5%, 2.5% to 3%, 2.5% to2.7%, 3.0% to 20%, 3.0% to 15%, 3.0% to 10.5%, 3.0% to 10%, 3.0% to9.5%, 3.0% to 9%, 3.0% to 8.5%, 3.0% to 8%, 3.0% to 7.5%, 3.0% to 7%,3.0% to 6.5%, 3.0% to 6%, 3.0% to 5.5%, 3.0% to 5%, 3.0% to 4.5%, 3.0%to 4%, 3.0% to 3.5%, 4.0% to 20%, 4.0% to 15%, 3.5% to 10.5%, 4.0% to10%, 4.0% to 9.5%, 4.0% to 9%, 4.0% to 8.5%, 4.0% to 8%, 4.0% to 7.5%,4.0% to 7%, 4.0% to 6.5%, 4.0% to 6%, 4.0% to 5.5%, 4.0% to 5%, 4.0% to4.5%, 5.0% to 20%, 5.0% to 15%, 5.0% to 10.5%, 5.0% to 10%, 5.0% to9.5%, 5.0% to 9%, 5.0% to 8.5%, 5.0% to 8%, 5.0% to 7.5%, 5.0% to 7%,5.0% to 6.5%, 5.0% to 6%, or 5.0% to 5.5%), 20% to 30%, 30% to 40%, 30%to 50%, or 50% to 60% as compared to before exposure of a stimulus. Fora particular device (e.g., a dressing), further tunability can beaccomplished by any processing or post-processing known in the art(e.g., by using one or more hydrophilic or hydrophobic coatings,hydrogels, foams, colloids, etc.), thereby providing further control ofone or more physical characteristics.

By “subject” is meant a human or non-human animal (e.g., a mammal).

By “treating” a disease, disorder, or condition in a subject is meantreducing at least one symptom of the disease, disorder, or condition byaffixing a device (e.g., a dressing) to the subject.

By “prophylactically treating” a disease, disorder, or condition in asubject is meant reducing the frequency of occurrence or severity of(e.g., preventing) a disease, disorder or condition by affixing a device(e.g., a dressing) to the subject prior to the appearance of a symptomof the disease, disorder, or condition.

Other features and advantages of the invention will be apparent from thefollowing Detailed Description and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D describe an exemplary method of tightening skin with atunable dressing. This method includes (FIG. 1A) forming holes throughthe dermal and epidermal layer, (FIG. 1B) applying a dressing on theholes in a tensionless state, in which the dressing adheres to the skinsurface, (FIG. 1C) activating the tension-regulation layer (orregulatable layer) of the dressing by, e.g., altering the dimension ofthe dressing (shrinking) and thereby applying a lateral compressionforce on the small holes, and (FIG. 1D) closing the holes by lateralcompression forces, thereby allowing for filling of any remaining spacein the holes with new tissue and completing the healing process.

FIG. 2 shows an exemplary dressing having a regulatable layer and anadhesive layer.

FIGS. 3A-3C describe an exemplary method of tightening skin in apreferred direction. This method includes (FIG. 3A) forming holes in theskin surface and either (FIG. 3B) tightening the skin withnon-directional tightening (i.e., directional tightening along both thex- and y-axis) or (FIG. 3C) tightening the skin with directionaltightening along the x-axis.

FIGS. 4A-4B show two exemplary dressings that provide non-directionaltightening (FIG. 4A) or directional tightening (FIG. 4B).

FIG. 5 shows an exemplary dressing that provides tightening along the x-and y-axis of the dressing, where tightening or contraction can becontrolled independently.

FIG. 6 describes the potential effect of pleating on the geometry ofholes formed in skin.

DETAILED DESCRIPTION

This invention relates to methods and devices for the tightening of skinand/or reduction of skin laxity by selectively opening or closing aplurality of small wounds formed by incision or excision of tissue.

For example, tissue excision can be performed by fractional ablation ofthe epidermal and/or dermal layer of the skin with a hollow coringneedle, by fractional laser ablation, by fractional radiofrequencyablation, and/or by fractional ultrasonic ablation. Various methods anddevices are proposed to close the small wounds, including tunable orsmart dressings that allow for titration of the tightening effect afterapplication to the skin of a patient.

In particular embodiments, the present invention provides one or more ofthe following advantages. First, the methods and devices herein enablevisualization of results in real time during the course of thetreatment. One can envision asking the patient for feedback in real timeduring the treatment and adjusting the tightening to the patientpreference. Second, the methods and devices herein are tunable, therebyallowing for titration of tightening after surgical hole or slitformation. For example, the tunable or smart dressings described hereinallow adjustment of the tightening intensity, direction, and spatialdistribution after the dressing has been applied or affixed to thepatient's skin. In another example, titratable tightening can beachieved by selectively closing or opening a subset of slits or holesproduced in an array. Third, the methods and devices herein requiresless skill than that of a surgeon. One can envision treatment ofpatients in an outpatient setting, rather than requiring an inpatient,surgical setting. Fourth, the methods and devices herein constituteminimally invasive techniques, which can provide more predictableresults and/or risk factors than that for more invasive techniques(e.g., plastic surgery) or non-invasive energy-based techniques (e.g.,laser, radiofrequency, or ultrasound). Fifth, the methods and devicesherein can allow for less discriminate methods for treating the skin byforming holes or slits because the methods and devices allow for morediscriminate control for closing such holes or slits. Sixth, the methodsand devices herein can allow for rapid closing of holes or slits aftertreating the skin (e.g., within a few seconds after treating skin, suchas within ten seconds), thereby minimizing the extent of bleeding and/orclotting within the holes or slits. Finally, the methods and devicesherein can be useful for maximizing the tightening effect whileminimizing healing time by optimizing tightening (e.g., by controllingthe extent of skin pleating, such as by increasing the extent of skinpleating for some applications or skin regions and by decreasing theextent of skin pleating for other applications or skin regions, asdescribed herein).

Devices for Closure of Holes

The present invention features methods and devices to tighten skinhaving one or more incised or excised tissue portions. In particular,exemplary devices include selectively opening or closing of holes and/orslits using a tunable dressing.

Tunable Dressings

The present invention features a tunable dressing having a regulatablelayer formed from any useful material(s) (e.g., any described herein,such as a shape-memory polymer). In particular, exposure of theregulatable layer to one or more external stimuli results in a change ina physical characteristic in the material(s). This change can extendacross the entire dressing (e.g., across the entire x-, y-, and/orz-direction of the dressing, including planar and non-planar changes) orin a portion or part of the dressing (e.g., at a localized area of thedressing, which has been locally exposed to a stimulus and therebyresults in a change in one or more physical characteristics in the x-,y-, and/or z-direction).

Further, the dressing can provide a variable tightening effect acrossthe entire dressing (e.g., varying degrees of tightening across theentire x-, y-, and/or z-direction of the dressing, including planar andnon-planar changes) or in a portion or part of the dressing (e.g.,varying degrees of tightening at a localized area of the dressing).

Any useful physical characteristic of the device (e.g., dressing) ormaterial in the device can be changed. Exemplary physicalcharacteristics include compression (or compressive force, e.g., lateralcompression), expansion (e.g., lateral expansion), tension (e.g., asmeasured by tensile stress), structure, size, porosity, surfacechemistry, bending modulus, fracture or failure strain, resilience,permeability, swelling ratio, elasticity (e.g., as measured by ultimatemodulus of elasticity from the end-portion of stress-strain curves thatis greater than 10 N/mm² (e.g., greater than about 15 N/mm², 20 N/mm²,25 N/mm², 30 N/mm², 35 N/mm², or 40 N/mm²) or between about 10 N/mm² and200 N/mm² (e.g., about 10 N/mm² and 150 N/mm², 10 N/mm² and 100 N/mm²,15 N/mm² and 200 N/mm², 15 N/mm² and 150 N/mm², 15 N/mm² and 100 N/mm2,20 N/mm² and 200 N/mm², 20 N/mm² and 150 N/mm², or 20 N/mm² and 100N/mm²)), electric conductivity, plasticity, resilience, resistance(e.g., as measured by creep resistance), strength (e.g., as measured byYoung's modulus, such as a Young's modulus that is greater than about1×10⁵ NM⁻² (e.g., greater than about 2.0×10⁵ N/m², 2.5×10⁵ N/m², 3.5×10⁵N/m², 4×10⁵

N/m², 4.5×10⁵ N/m², 5×10⁵ N/m², 6×10⁵ N/m², 7×10⁵ N/m², 8×10⁵ N/m²,6×10⁵ N/m², or 10×10⁵ N/m²), tensile strength, such as a tensilestrength that is greater than about 2 N/mm² (e.g., greater than about 5N/mm², 7 N/mm², 10 N/mm², 15 N/mm², 17 N/mm², 20 N/mm², 25 N/mm², 27N/mm², 30 N/mm², or 35 N/mm²) or between about 5 N/mm² and 40 N/mm²(e.g., between about 15 N/mm² and 30 N/mm², 15 N/mm² and 35 N/mm², 10N/mm² and 30 N/mm², or 10 N/mm² and 35 N/mm²), compressive strength,impact strength, or yield strength), stress (e.g., as measured bycompressive stress, shear stress, or tensile stress), load (e.g., loadper millimeter width of at least 0.1 Newtons at a strain of at least0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3,0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or higher), strain (e.g., as measured bydeflection, deformation, strain at failure, or ultimate strain(extension before rupture), e.g., greater than about 30% (e.g., greaterthan about 40%, 50%, 60%, 70%, 75%, 80%, 90%, 95%, 100%, 110%, 115%, or120%) or from about 30% to 130% (e.g., about 30% to 120%, 30% to 115%,30% to 110%, 30% to 100%, 30% to 95%, 30% to 90%, 30% to 85%, 30% to80%, 30% to 75%, 30% to 70%, 30% to 65%, 30% to 60%, 30% to 55%, 30% to50%, 35% to 130%, 35% to 120%, 35% to 115%, 35% to 110%, 35% to 100%,35% to 95%, 35% to 90%, 35% to 85%, 35% to 80%, 35% to 75%, 35% to 70%,35% to 65%, 35% to 60%, 35% to 55%, 35% to 50%, 40% to 130%, 40% to120%, 40% to 115%, 40% to 110%, 40% to 100%, 40% to 95%, 40% to 90%, 40%to 85%, 40% to 80%, 40% to 75%, 40% to 70%, 40% to 65%, 40% to 60%, 40%to 55%, 40% to 50%, 50% to 130%, 50% to 130%, 50% to 120%, 50% to 115%,50% to 110%, 50% to 100%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to80%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 50% to 55%, 60% to130%, 60% to 120%, 60% to 115%, 60% to 110%, 60% to 100%, 60% to 95%,60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%,70% to 130%, 70% to 120%, 70% to 115%, 70% to 110%, 70% to 100%, 70% to95%, 70% to 90%, 70% to 85%, 70% to 80%, 70% to 75%, 75% to 130%, 75% to120%, 75% to 115%, 75% to 110%, 75% to 100%, 75% to 95%, 75% to 90%, 75%to 85%, 75% to 80%, 80% to 120%, 80% to 115%, 80% to 110%, 80% to 100%,80% to 95%, 80% to 90%, or 80% to 85%)), and other parameters.

Further, the extent or intensity of the physical characteristic can beincreased or decreased after exposure to one or more stimuli. Exemplaryphysical characteristics include an increase in tension, a decrease intension (e.g., of the dressing), an increase in compressive force (e.g.,lateral compressive force that is exerted by the dressing), a decreasein compressive force (e.g., lateral compressive force that is exerted bythe dressing), compression in one or more directions of the dressing,and/or expansion in one or more directions of the dressing.

The change in one or more physical characteristics can be optimizedbased on the desired response to a stimulus, location of the skin regionto be treated, or any other useful parameter. For instance, the changein physical characteristic can be optimized for placement in the eyeregion, where the eye region includes Langer lines having particulardirections, and the directionality of compression or expansion exertedby the dressing can be perpendicular to such Langer lines to promoteskin tightening. Further, optimization that takes into account Langerlines can be utilized on any area of the body. Langer lines correspondto the orientation of native collagen fibers in the dermis. The closingof ablations (including micro-ablations) following Langer lineorientation maximizes wound closure efficiency and tightening, and maybe applied to any area of the body.

The directionality of the change in the physical characteristics,relative to the device (e.g., dressing) or skin region, can also beoptimized. In particular embodiments, the direction of skin tighteningis determined by the directionality of the physical characteristicchange. For instance, the direction of the tensile force or compressiveforce can be in the x-, y-, and/or z-direction with respect to thedevice or skin region (see, e.g., FIGS. 1A-1D for the x-axis, z-axis,and x-z plane for an exemplary device relative to the skin portion; andFIGS. 3A-3C for the x-axis, y-axis, and x-y plane for an exemplarydevice relative to the skin portion). An exemplary device providingdirectional tightening (e.g., directional compression and/or expansion)is provided in FIGS. 4 and 5. In particular embodiments, the device(e.g., a dressing having a regulatable layer and/or an unstretchedlayer) contracts or expands in one or more directions (e.g., in planarand/or non-planar directions) after exposure to a stimulus. Such adevice may be used for any method described herein, such as to reducepleating. In one particular embodiment, the device compresses the skinin one direction (e.g., along the x-axis) as it expands in anotherdirection (e.g., along the y-axis). In this instance, the surface areacovered by the dressing may be reduced or not.

The intensity of the change in the physical characteristic(s), ascompared to before exposure to one or more stimuli, can also beoptimized. Such optimization can include selection of particularmaterials (e.g., one or more particular shape-memory polymers or alloys)or combinations of such materials to produce the intended effect (e.g.,a combination of a rigid polymer with one or more particularshape-memory polymers or alloys), as well as arrangement (e.g.,geometric or random arrangement) of such material(s) within a singlelayer in a device (e.g., within a single regulatable layer) or inseparate multiple layers (e.g., in more than one regulatable layers,such as one, two, three, or more layers) in a device to produce theintended directionality and/or intensity of the physicalcharacteristic(s).

The external stimulus to activate or induce the physical characteristiccan be any useful stimulus. Exemplary stimulus includes a change intemperature, pH, light, moisture, solvent or chemical exposure, electricfield, and/or magnetic field. In particular embodiments, the deviceincludes one or more materials (e.g., in one or more layers) that can beactivated by different external stimuli. An exemplary device is providedin FIG. 5, where the regulatable layer includes a first polymer (i.e.,responding to stimulus A) and a second polymer (i.e., responding tostimulus B), where stimulus A and stimulus B are different types ofstimuli (e.g., temperature and light) or different characteristics ofthe same stimulus (e.g., two different wavelengths of light). The firstand second polymer can be the same polymer that has been modified,shaped, or processed to respond to different stimuli or differentpolymers having different chemical characteristics.

Furthermore, the change in physical characteristic or exposure of astimulus can include the entire device or only a portion of the device.For example, the entire dressing can be exposed to an external stimulusto induce a change in compression over the entire skin region to whichthe dressing is affixed. Although the change in compression can occurover the entire skin region, the extent or intensity of compression canvary along the x-, y-, and/or z-axes or within the xy-, xz-, yz-, and/orxyz-planes of the skin region. In another example, the dressing can belocally exposed to an external stimulus to induce a change incompression over a portion of the device (i.e., thereby resulting in achange in compression over a portion of the skin region). In particularembodiments, the device (e.g., a dressing having a regulatable layerand/or an unstretched layer) contracts or expands in one or moredirections (e.g., in planar and non-planar directions) in a portion ofthe area of the device after exposure to a stimulus. Such a device maybe used for any method described herein, such as to reduce pleating.

Tunability of the dressing can provide numerous benefits. For instance,such tunability can allow for real-time control of compressing and/orexpanding the dressing after affixation. This level of control can allowfor personalized treatment of the patient based on the disease,disorder, or condition to be treated; the optimal cosmetic effect to beachieved; the optimal closure process to be achieved; and/or the timingand extent of the healing process observed for the particular patient.Furthermore, tunability can allow for less discriminate control over howthe incisions or excisions in the skin region are made, as well as morediscriminate control over selectively closing or opening the incisionsor excisions.

The tunable dressing can be affixed to the entire treated skin region orin a portion of the treated skin region. Directional or non-directionaltightening can be achieved by producing a geometric arrangement ofincisions and/or excisions that are treated similarly. Alternatively,such tightening can be achieved by a non-geometric arrangement ofincisions and/or excisions in which only some of the incisions and/orexcisions are opened or closed using a tunable dressing.

The tunable dressing can include an adhesive layer (e.g., formed fromany adhesive material described herein). The adhesive layer can becontinuous (i.e., a continuous layer of one or more adhesive materialsattached to the proximal surface of a dressing) or discontinuous (i.e.,a non-continuous layer of one or more adhesive materials attached to theproximal surface of a dressing). The adhesive layer can include anyuseful arrangement of the adhesive material. For instance, the adhesivelayer can be tunable and allows for controlled compression or expansion.In some embodiments, an adhesive layer includes a random, non-geometric,or geometric array of an adhesive material for tunability. In particularembodiments, the array allows for directional or non-directionalcompression and/or expansion as the dressing compresses and/or expands.In particular embodiments, the adhesive layer is discontinuous andincludes an array of an adhesive material (e.g., an array of dots, whereeach dot gets closer together as the dressing compresses and each dotgets further apart as the dressing expands). Exemplary adhesivematerials are described herein and include materials that promotecollagen cross-linking, such as riboflavin or Rose Bengal, syntheticglues (e.g., cyanoacrylate, polyethylene glycol, orgelatin-resorcinol-formaldehyde), or biologic sealants (e.g.,albumin-based or fibrin-based sealants that promote clotting).

The material(s) of the device can include any useful arrangement orform. Exemplary arrangements include a geometric arrangement of one ormore materials within a single layer (e.g., a linear array or a grid ofone or more materials in a single regulatable layer; or a linear arrayor a grid of one or more adhesive materials in a single adhesive layer);a geometric arrangement of one or more materials within multiple layers(e.g., in a multilayer dressing having more than one layer, where eachlayer includes a linear array or a grid of one or more materials andeach linear array or grid is optimized for directional compression orexpansion); a random, non-uniform arrangement of one or more materialsin a single layer or across a plurality of layers; or combinationsthereof. In some embodiments, a layer includes a first array of a firstmaterial and a second array of a second material, where each array has ageometric arrangement that promotes directional or non-directionalcompression or expansion. In particular embodiments, the first array isorthogonal to the second array. The materials can also be in any usefulform, e.g., a film, a membrane (e.g., as in temperature shrink wrap), oran actuator having more complex geometries. In other embodiments, anadhesive layer includes an array of an adhesive material, where thearray has a random, non-geometric, or geometric arrangement that allowsfor directional or non-directional compression or expansion as theregulatable layer or dressing compresses and/or expands. In particularembodiments, the adhesive layer is discontinuous and includes an arrayof an adhesive material (e.g., an array of dots of an adhesivematerial).

The material(s) of the device can optionally include one or moreactuators in any useful arrangement or form. Such actuators can beembedded in one or more materials and in one or more layers (e.g., inthe regulatable layer and/or the adhesive layer). Furthermore, theactuators can allow for uniform, non-uniform, or variable control (e.g.,compression and/or expansion) across the entire device or in a portionof the device. Thus, actuators can be embedded across the entire device,in a portion of the device, in one layer, or in multiple layers. Inparticular embodiments, the stimulus-responsive material includes one ormore actuators that respond to one or more stimuli, where the materialincludes a plurality of one type of actuator or a plurality of differentactuators. The actuators in each layer can be arranged in any usefulrandom, non-geometric, or geometric arrangement. Alternatively, theactuators can be arranged within multiple layers (e.g., in a multilayerdressing having more than one layer, where each layer includes a lineararray or a grid of one or more actuators and each linear array or gridis optimized for directional compression or expansion); a random,non-uniform arrangement of one or more actuators in a single layer oracross a plurality of layers; or combinations thereof. Exemplarymaterials including one or more actuators are described herein.

The material(s) or layer(s) in a device (e.g., a dressing) can includean unstretched layer (e.g., including any material described herein) andan adhesive layer. The unstretched layer can include one or moreunstretched materials, including those having sufficient rigidity tohinder stretching and those having one or more stretchable polymers thatare not stretched prior to affixing to a skin region. The material(s) orlayer(s) in a device (e.g., a dressing) can include an adhesive layer, aregulatable layer, as well as one or more additional, optional layers orfasteners (e.g., staples, sutures, etc.). Exemplary optional layersinclude an occlusion layer (e.g., to control humidity and/or promotewound healing), an absorption layer (e.g., to absorb wound exudate), areinforcement layer (e.g., to reinforce the layer and optionally formedfrom low-density polyethylene (LDPE), fluorinated ethylene propylene(FEP), or nylon), and/or a delivery layer (e.g., to delivery one or moretherapeutic agents, as described herein).

The device (e.g., dressing) can optionally include an applicator, asdescribed herein. In some embodiments, the applicator is a frame or anyother useful structure that provides sufficient support to the tunabledressing and/or provides a sterile method to affix the tunable dressingto the treated skin region. In other embodiments, the applicator isconfigured to attach to an apparatus that forms one or more incisionsand/or excisions, where the applicator allows for releasing and/oraffixing the tunable dressing after the formation of such an incision orexcision (e.g., within about 30, 25, 20, 15, 10, 5, 3 seconds or lessafter forming an incision or excision).

The device can be of any cosmetically appealing color, shape, and/ormaterial. For example, the tunable dressing can be provided in a skintone color or is transparent or semi-transparent. Such transparent orsemi-transparent dressings can additionally be helpful forvisualization, e.g., for real-time tunability of the dressing and/or foraffixing the dressing to the treated skin region.

Exemplary tunable dressings and materials for constructing such dressingare described herein.

Testing of Devices

To optimized function of any of the devices described herein, theappropriate force (e.g., compressive, tensile, and/or lateral force)and/or geometric arrangement of the device (e.g., a dressing) can betested by any useful metric. Exemplary metrics include any usefulendpoint, such as presence or absence of melanocytes, melanin inkeratinocytes, collagen production, elastin, scarring and/or infection,fibroblast activity, inflammation, macrophage and/or leukocyterecruitment, or the relative thickness of the papillary dermis and/orepidermis; melanin index, which is a unitless variable that quantifiesthe concentration of melanin in skin (e.g., by obtaining a reflectancespectrum and determining the slope of the log of the inverse reflectancevalues for wavelengths between 620 and 700 nm); erythema index, which isa unitless variable that quantifies the concentration of melanin and/orhemoglobin in skin (e.g., by obtaining an absorption spectrum anddetermining the log of the ratio of the reflectance at 635 nm and at 565nm, such as by using a commercially available reflectance instrumentfrom Diastron (Hampshire, U.K.)); transepidermal water loss, whichmeasures the quantity of water that passes from the inside of a bodythrough the epidermal layer; the Glogau wrinkle assessment scale with ascoring system of type I (no wrinkles), type II (wrinkles in motion),type III (wrinkles at rest), and type IV (only wrinkles), as describedin Glogau, “Aesthetic and anatomic analysis of the aging skin,” Semin.Cutan. Med. Surg. 15(3):134-138 (1996); and/or the Fitzpatrick wrinkleassessment scale (FWAS) or modified FWAS (MWAS) with a scoring system of0 (no wrinkle: no visible wrinkle, continuous skin line), 0.5 (veryshallow yet visible wrinkle), 1 (fine wrinkle: visible wrinkle andslight indentation), 1.5 (visible wrinkle and clear indentation withless than 1 mm wrinkle depth), 2 (moderate wrinkle: clearly visiblewrinkle with 1 mm to 2 mm wrinkle depth), 2.5 (prominent visible wrinklewith more than 2 mm and up to 3 mm wrinkle depth), and 3 (deep wrinkle:deep and furrow wrinkle with more than 3 mm wrinkle depth).

Further Processing of Devices

The devices (e.g., dressings) can be further processed prior to affixingto the subject. Exemplary processes include sterilization (e.g., withultrasound, ultraviolet light, heat, and/or plasma); treatment with oneor more antimicrobials (e.g., treatment with chlorhexidine gluconate orsilver, such as a silver nitrate or Ag⁺ in one or more useful carriers,as described herein); and/or treatment with one or more agents, e.g., toform a coating on the dressing, where exemplary agents include abiocompatible matrix (e.g., those including at least one of collagen(e.g., a collagen sponge), low melting agarose (LMA), polylactic acid(PLA), and/or hyaluronic acid (e.g., hyaluranon)), a photosensitizer(e.g., Rose Bengal, riboflavin-5-phosphate (R—5-P), methylene blue (MB),N-hydroxypyridine-2-(1H)-thione (N-HTP), a porphyrin, or a chlorin, aswell as precursors thereof), a photochemical agent (e.g., 1,8naphthalimide), a fibrin sealant, a cyanoacrylate adhesive, or a tissueglue composed of a mixture of riboflavin-5-phosphate and fibrinogen

Methods of Skin Tightening

The present invention relates to various methods and devices (e.g.,dressings) used to selectively open or close incisions and/or excisions(e.g., all or a portion of such incisions, such as microslits, and/orexcisions, such as holes) formed in the skin region by the incised orexcised tissue portions. The devices can be affixed to the entiretreated skin region or in a portion of the treated skin region, whichallow for directional or non-directional tightening by producing ageometric or non-geometric arrangement of incisions and/or excisionsthat are treated similarly or differently. Further, the devices canprovide uniform or non-uniform compression and/or expression across theentire device or a portion thereof. Accordingly, these methods anddevices can result in reducing the skin surface and/or tightening of theskin.

The methods can include contraction or expansion in one or moredirections in at least a portion of the device (e.g., the dressing). Themethods include, for example, affixing a device to a skin region havinga plurality of incised tissue portions and/or excised tissue portions(e.g., where at least two of said tissue portions has at least onedimension that is less than about 1 mm or an areal dimension that isless than about 1 mm²). The device provides contraction or expansion ofthe skin region in one or more directions (e.g., in the x-, y-, z-, xy-,xz-, yz-, and/or xyz-directions, as described herein), where suchcontraction or expansion can be uniform or non-uniform. Furthermore,contraction or expansion arises by exposing an affixed device to one ormore external stimuli (e.g., any described herein) that results in achange in a physical characteristic of the device. In addition, suchcontraction and/or expansion can be adjusted after affixing the device.For example, after treating the skin and affixing the device, the devicecan result in expansion of the skin region and then later exposed to anexternal stimulus to further expand or to compress the skin region. Inthis manner, the device is tunable.

The present invention also includes methods of tightening skin in apreferred direction. An exemplary method is provided in FIGS. 3A-3C,which show (in FIG. 3A) the skin surface (top view, x-y plane) beforeclosure of the small holes and (in FIG. 3B) after non-directionaltightening or (in FIG. 3C) after directional tightening along thex-axis. This method is described in detail herein. Directionaltightening of the skin (e.g., by compression and/or expansion exerted bythe device) can be optimized by using one or more materials in one ormore layers of the device. Such compression and/or expansion can becontrolled independently (e.g., by use of one or more stimuli).

The present invention also includes optimizing the dimension of theincised or excised tissue portions to promote wound healing. Exemplarydimensions include circular and non-circular holes, such as ellipticalholes (e.g., as viewed from the xy-plane). Non-circular holes can beformed by using an apparatus having a non-circular cross-section (e.g.,a blade or a tube, such as a hollow tube, having a non-circularcross-section) or by pre-stretching the skin before treatment with anapparatus having a circular cross-section (e.g., a circular coringneedle generates an elliptical hole in a non-stretched skin). In someembodiments, the long axis of the ellipse is perpendicular to thepre-stretching direction, where the elliptical hole can generate skintightening preferentially in the direction of the short axis of theellipse. Accordingly, the devices of the invention (e.g., a dressing, asdescribed herein) can be affixed to a skin portion including one or moreelliptical holes or one or more incised or excised tissue portionshaving one or more elliptical geometries.

The methods and devices herein can allow for less discriminate methodsfor treating the skin by forming holes or slits because the methods anddevices allow for more discriminate control for closing or opening suchholes or slits. For instance, tunable dressings allow for real-timecontrol for compressing or expanding holes or slits. Exemplary modes ofcontrol include the extent of compression or expansion, thedirectionality of compression or expansion (e.g., in the x-, y-, z-,xy-, yz-, xz-, or xyz-direction), and/or timing of applying thecompression or expansion (e.g., within a few seconds, such as within 30,20, 15, 10, 5, 3 seconds, or less).

Control of Skin Pleating

Furthermore, the methods and devices of the invention can be used tocontrol skin pleating. For example, when using dressing to compress theskin and close holes and/or slits, it may be advantageous to apply anoptimal compression level that can be adjusted during the treatmentperiod and after affixing the dressing. During the setting of thetissue, skin pleating can be beneficial in some instances and should beavoided in other instances. After the excision or incision, the tissuecan be compressed or expanded in order to set the tissue. In particularexamples, the setting time may be as short as 2-4 days, and the tunabledressing provides compression or expansion prior to this setting time.Accordingly, the methods and devices or the invention can be used tocontrol the level of compression and/or expansion exerted by the deviceto increase and/or decrease the extent of skin pleating.

The state of the tissue can provide feedback about the optimalcompression level, such that tissue pleating can be controlled. Tissuepleating may affect the wound healing process, where FIG. 6 shows anexemplary effect of pleating on hole geometry. Furthermore, in someinstances, pleating may prevent conformal adhesion of the device withthe treated skin region, thereby affecting the function of a wounddressing that requires contact with the skin. Accordingly, pleating canbe controlled by inspecting the skin periodically and adjusting thetunable dressing affixed to the skin region (e.g., by exposure of one ormore external stimuli). Alternatively, the dressing can control pleatingby having limited flexibility (e.g., by including one or more rigidmaterials or unstretched materials, as described herein) or limitedflexibility in particular areas and/or directions. In one particularexample, pleating can be controlled by minimizing the size of thecompressed area. For example, the methods include the use of a tunabledressing having multiple, smaller compression areas proximal to eachother, separated and/or surrounded by non-compressed areas. Tunabledressings that exploit this compression area format are also included inthe invention.

The methods and devices for skin tightening can also be optimized forconforming to uneven skin surfaces, whether such surfaces arise from aparticular disease or condition (e.g., any described herein) or from theanatomical location of the skin region (e.g., in the brow, chin, orbreast regions). Such unevenness can occur in any direction or plane,including non-planar and planar unevenness. In some embodiments, thetunable dressing includes one or more materials that allow forcontraction or expansion of the skin region in one or more directions(e.g., in the x-, y-, z-, xy-, xz-, yz-, and/or xyz-directions, asdescribed herein), as well as in planar and non-planar directions (e.g.,in the xy-, xz-, yz-, and/or xyz-planes). When treating uneven skinsurfaces, tissue pleating can be a particular concern that should becontrolled. Thus, the methods, devices, and tunable dressing describedherein can be useful for optimizing compression and/or expansion levelsin any useful direction(s) for treating uneven skin surfaces, whilecontrolling pleating.

Materials

The methods, devices, and apparatuses of the invention can include anyuseful materials. In a tunable dressing, the regulatable layer caninclude one or more stimulus-responsive materials (e.g., a shape-memorymaterial, a shape-memory polymer, a shape-memory alloy, athermal-responsive material, a pH-responsive material, alight-responsive material, a moisture-responsive material, asolvent-responsive or chemical exposure-responsive material, an electricfield-responsive material, a magnetic field-responsive material, anactuator-embedded material, and/or an unstretched material). Theadhesive layer can include one or more adhesive materials (e.g.,pressure sensitive adhesives).

The materials can include arise from any useful mechanism forcompressing and/or expanding the device, as well as any useful stimulus.Such mechanisms include mechanical, hydraulic, and/or pneumatic modes ofoperation. Exemplary stimulus includes a change in temperature, pH,light, moisture, solvent, chemical exposure, electric field, and/ormagnetic field, which can optionally result in mechanical, hydraulic,and/or pneumatic tuning.

The materials can be of any useful form. Exemplary forms include anemulsion, a fiber, a film, a foam, a hydrogel, a solution, a laminate,or any other form that can be further processed, such as shaped, cast,extruded, molded (e.g., by blow molding, injection molding, or resintransfer molding), woven, cross-linked, deposited, laminated, and/orspun (e.g., by wet spinning, electrospinning, and/or melt spinning) toany useful article (e.g., a dressing or one or more layers within adressing).

Shape-Memory Materials

Shape-memory materials (SMMs) can change their physical conformation (orshape) under an external stimulus (e.g., a thermal stimulus). Forexample, an article formed from an SMM or coated with an SMM can possessa first, desired shape and a second, temporary shape. When the SMM isregulatable by temperature, switching between these two shapes isachieved by heating or cooling above the glass or melting transitiontemperature of the SMM. SMMs may have a completely reversible transition(e.g., in a material that returns to its original shape) or a partiallyreversible transition with hysteresis (e.g., resulting in a materialrequiring additional energy to return to its original shape). SMMs canhave multiple external stimulus responses, such as responses to bothtemperature and light or temperature and magnetic fields.

SMMs include both shape-memory polymers (SMPs) and shape-memory alloys(SMAs). SMPs can be in any useful form, such as in the form of theparent polymer chain, gels, hydrogels, emulsions, or micelles. ExemplarySMPs include shape-memory polyurethane (e.g., a poly(propylene glycol)(PPG), 4,4′-diphenylmethane diisocyanate (MDI), and dimethylolpropionicacid (DMPA) (PPG/MDI/DMPA) copolymer, where —NCO is optionallyend-capped with methyl ethyl ketoxime (MEKO), or polymers includingdimethyloldihydroxyethylene urea (DMDHEU) and/or 1,2,3,4-butanetetra-carboxylic acid (BTCA)); a poly(ethyleneterephthalate)/poly(caprolactone) (PET/PCL) block copolymer (e.g.,optionally crosslinked with maleic anhydride, glycerin, or dim ethyl5-isophthalate); a polyethylene terephthalate/polyethylene oxide(PET/PEO) block copolymer; an ABA triblock copolymer made frompoly(2-methyl-2-oxazoline) and polytetrahydrofuran; a polystyrene andpoly(1,4-butadiene) (PS/PBD) block copolymer; a polyethyleneglycol/4,4′-diphenylmethane diisocyanate/pentaerythritol (PEG/MDI/PE)copolymer; polynorbornene ((C₇H₁₀)_(x) or Norsorex®, available fromAstrotech Advanced Elastomer Products GmbH, Vienna, Austria);organic-inorganic hybrid polymers including polynorbornene unitspartially substituted by polyhedral oligosilsesquioxane (FOSS); anacrylate-based polymer; a styrene-based polymer; an epoxy-basedpolymer); and shape-memory fibers (e.g., oligomers prepared with polyolas the soft segment and small size diols and MDI as the hard segment).

Exemplary SMAs include a nickel-titanium (NiTi) alloy (e.g., Nitinol™,available from Nitinol Devices & Components, Inc., Fremont, Calif., ofapproximately 55% Ni); a nickel-titanium-niobium (NiTiNb) alloy; anickel-iron-gallium (NiFeGa) alloy; a nickel-manganese-gallium (NiMnGa)alloy; a copper-aluminum-nickel (CuAlNi) alloy (e.g., 14/14.5 wt. % Aland 3/4.5 wt. % Ni); a copper-zinc (CuZn) alloy (e.g., 38.5/41.5 wt. %Zn); a copper-tin (CuSn) alloy (e.g., approximately 15 at. % Sn); acopper-zinc-aluminum (CuZnAl) alloy; a copper-zinc-silicon (CuZnSi)alloy; a copper-zinc-tin (CuZnSn) alloy; a copper-manganese alloy (e.g.,5/35 at. % Cu); a gold-cadmium (AuCd) alloy (e.g., 46.5/50 at. % Cd); asilver-cadmium (AgCd) alloy (e.g., 44/49 at. % Cd); an iron-platinum(FePt) alloy (e.g., approximately 25 at. % Pt); aniron-manganese-silicon (FeMnSi) alloy (e.g., approximately 25 at. % Pt);a cobalt-nickel-aluminum (CoNiAl) alloy; a cobalt-nickel-gallium(CoNiGa) alloy; or a titanium-palladium (TiPd) alloy.

SMMs can also include shape-memory composites (SMC) and shape-memoryhybrids (SHC). SMCs and SMHs are dual component systems that include atleast one SMM integrated with conventional materials. Exemplaryconventional materials include those useful for preparing wound caredressings, such as any described herein and include, e.g., alginate,benzyl hyaluronate, carboxymethylcellulose, cellulose acetate, chitosan,collagen, dextran, epoxy, gelatin, hyaluronic acid, hydrocolloids, nylon(e.g., nylon 6 or PA6), pectin, poly (3-hydroxyl butyrate-co-poly(3-hydroxyl valerate), polyacrylate (PA), polyacrylonitrile (PAN),polybenzimidazole (PI31), polycarbonate (PC), polycaprolactone (PCL),polyester (PE), polyethylene glycol (PEG), polyethylene oxide (PEO),PEO/polycarbonate/polyurethane (PEO/PC/PU), poly(ethylene-co-vinylacetate) (PEVA), PEVA/polylactic acid (PEVA/PLA), poly (ethyleneterephthalate) (PET), PET/poly (ethylene naphthalate) (PET/PEN)polyglactin, polyglycolic acid (PGA), polyglycolic acid/polylactic acid(PGA/PLA), polyimide (PI), polylactic acid (PLA), poly-L-lactide (PLLA),PLLA/PC/polyvinylcarbazole (PLLA/PC/PVCB), poly ((3-malicacid)-copolymers (PMLA), polymethacrylate (PMA), poly (methylmethacrylate) (PMMA), polystyrene (PS), polyurethane (PU), poly (vinylalcohol) (PVA), polyvinylcarbazole (PVCB), polyvinyl chloride (PVC),polyvinylidenedifluoride (PVDF), polyvinylpyrrolidone (PVP), silicone,rayon, or combinations thereof.

Exemplary SMCs include dual component systems including SMM materials incontact with conventional materials, such that the conventional materialapplies a force to bend the SMM absent an external stimulus. Upon theaddition of an external stimulus, the SMM changes shape, thus overcomingthe force applied from the conventional material. The resulting shapetransition moves both the SMM and conventional components. In addition,SMHs exhibit the characteristic shape transitions of SMM but areconstructed from conventional materials (e.g., non-shape-memorymaterials). Exemplary SMHs include dual region plastic materialsconstructed of two conventional polymers layers, where the materialbends in response to temperature changes due to the difference inthermal expansion between the two plastic layers. Additional exemplarySMC and SHC materials can be found in, e.g., in Huang et al., “Shapememory materials,” Materials Today 13:54-64 (2010), which is herebyincorporated by reference in its entirety.

Thermal-Responsive Materials

Thermal-responsive materials can change their physical and chemicalproperties upon changes in temperature. The transition temperature isthe temperature at which the polymer's characteristics change andincludes a lower critical solution temperature (LOST) or an uppercritical solution temperature (UCST). A common, exemplary response totemperature change is a transition in the hydrophilic/hydrophobiccharacter of the material. A transition to a more hydrophobic stateresults from changes in the polymer's ability to hydrogen bond with thesurrounding environment (e.g., a solvent or solution). For athermal-responsive polymer dissolved in solution, the temperatureresponse can result in a transition in the polymer's conformation andsolvent interaction. This transition includes an expanded state withextensive solvent interaction and a contracted state with limitedsolvent interaction. In the contracted state, the thermal-responsivepolymer will become insoluble and precipitate from solution.

The same above-described transition can occur in other forms (e.g., ingels, such as in hydrogels in which the cross-linked polymer is swollenby a solvent, or in copolymers). Upon exposure to a temperaturetransition, the conformation of the polymer network changes, thusresulting in reduced solvent interactions and causing a reduction in thegel's volume. Often the transition temperature is independent of thepolymer's molecular weight. The transition temperature can be modifiedwith changes to the solvent system. For example, the addition ofcosolvents or salts can increase or decrease the transition temperature.For copolymers, the transition temperature in aqueous environments isgenerally decreased with the addition of more hydrophobic co-monomers orpolymer modifying groups. Alternatively, the transition temperature isgenerally increased by the addition of more hydrophilic co-monomers orpolymer modifying groups.

Exemplary thermal-responsive materials includepoly-N-isopropylacrylamide (poly-NIPAAm, LCST at 32-37° C.);poly-N-vinylcaprolactam (LCST at 25-35° C.); poly-N,N-diethylacrylamide(LCST at 25¬32° C.); other polyalkylacrylamides and co-polymers ofpolyalkylacrylamides; polyethylene glycol; polyethylene oxide (PEO, LCSTat about 85° C.); polypropylene oxide (FPO); polymethylvinyl ether (LCSTat 34-38° C.); and PEO-PPO copolymers. Exemplary thermal-responsive gelsor hydrogels include copolymer networks of includepoly-N-isopropylacrylamide, poly-N-vinylcaprolactam,poly-N,N-diethylacrylamide, and other polyalkylacrylamides with across-linker, such as methylene bisacrylamide. Such thermal-responsivematerials can be provided in any form, such as heat shrink films.

pH-Responsive Materials

pH-responsive materials can change their physical and chemicalproperties upon changes in pH. A transition can arise from increasedcharge density resulting from protonation or deprotonation of a polymeror from decreased charge density resulting from neutralization of thepolymer. In general, increasing the charge density results in increasedhydrophilicity, which in turn promotes interactions with water, polarsolvents, or salts. Decreasing charge density typically makes thepolymer more hydrophobic and reduces the interactions with water, polarsolvents, and salts.

The nature of the pH transition results from the type of acid/basefunctionalities present in the material. For example, the presence ofamine functionalities (e.g., moieties with a high pKa) results in highercharge densities as the pH decreases and neutralization of the charge asthe pH increases. Conversely, the presence of carboxylic acidfunctionalities (e.g. moieties with a low pKa) results in higher chargedensities as the pH increases and neutralization of the charge as the pHdecreases. For a pH-responsive polymer in solution, a transition from ahigher charge density to a lower charge density (e.g., neutralization ofcharge) can result in the polymer becoming insoluble and precipitatingfrom solution. An insoluble pH-responsive polymer can dissolve intowater as the charge density is increased (e.g. increasing pH for acarboxylic acid moiety containing polymer). The same pH-responsetransition can occur in numerous forms, such as gels or hydrogels.Typically, an increasing charge density causes the gel network to swellwith water, polar solvents, or salts, thus expanding the gel's volume.Conversely, the neutralization of charge results in a reduction of thegel volume due to the elimination of water, polar solvents or salts fromthe network.

Exemplary pH-responsive polymers include polyacrylic acid,polymethacrylic acid, and methacrylic acid/methyl methacrylatecopolymers (Eudragit®, Evonik Industries AG); copolymers of polyacrylicacid and polyvinyl alcohol (PAA/PVA); carboxylic acid derivatives ofstyrene; derivatives of cellulose such as carboxymethylethylcellulose,cellulose acetate-phthalate and diethylaminoethyl cellulose;diethylaminoethyl methacrylate/methyl methacrylate or butyl methacrylatecopolymers (e.g., insoluble at pH 7, soluble at acidic pH);polypyridine; polyallylamine, polyvinylamine, chitosan, and otherpolyamines; as well as N-dimethylaminoethyl methacrylate, biodegradablecopolymers of N,N-dimethylacrylamide, N-tert-butyl acrylamide andN-methylacryoylglycylglycine p-nitrophenyl ester. ExemplarypH-responsive gels or hydrogels include methacrylic acid/methylmethacrylate polymer networks crosslinked with a bifunctionalmethacrylate, such as 1,4-butanediol dimethacrylate, carboxylic acidderivatives of styrene crosslinked with divinylbenzene; cellulosederivatives crosslinked with multifunctional cross-linking agents suchas butanediol diglycidylether; as well as copolymers of polyacrylic acidand polyvinyl alcohol cross-linked with a divinyl group such as1,4-butanediol dimethacrylate. Exemplary pH-sensitive materials arefound, e.g., in Galaev et al., Russian Chem. Reviews 64: 471-489 (1995),which is hereby incorporated by reference in its entirety.

Light-Responsive Materials

Light-responsive materials can change their physical and chemicalproperties upon exposure to electromagnetic radiation. Typically,moieties within the polymer structure undergo a change in response tolight of a particular energy. The light provides energy for the moietyto overcome activation energy barriers and transition into a differentconformation or state. For example, a copolymer incorporating anazobenzene chromophore has a lower dipole moment (e.g., is less polar)in the trans conformation around the azo double bond. The azobenzenemoiety provides a light sensitive “switch,” which provides the responseto external stimulus. Upon irradiation with light, the double bond canisomerizes to the cis conformation, thus increasing the dipole moment(e.g., making the polymer more polar). The increase in polarity canresult in increased solubility in polar solvents. This phenomenon isobserved with a dimethylacrylamide-4-phenylazophenylacrylate (7.5 mol %)copolymer. At a temperature slightly above the LOST, the solution isgenerally cloudy. However, upon UV irradiation, the copolymer's LCST isreduced below the environmental temperature and the solution becomesclear as the copolymer dissolves. Exemplary light-sensitive polymers arefound, e.g., in Galaev et al., Russian Chem. Reviews 64:471-489 (1995),which is hereby incorporated by reference in its entirety.

Light-responsive polymers include those having one or more of thefollowing light-responsive switches: cinnamic acid, cinnamylidene aceticacid, azobenzene chromophores (e.g., 4-phenylazobenzene),triarylmethylcyanide, stilbene, or quinone-methide moieties.

Moisture-Responsive Materials

Moisture-responsive materials can change their physical and chemicalproperties upon a change in the environmental humidity or water content.This transition generally involves an increasing or decreasingassociation with other components in the medium following exposure towater. Essentially, water displaces or increases the volume of theexisting medium thus causing changes commiserate with the polymer'shydrophilicity. For example, the grafted polymer, polymethacrylicacid-graft-polyethylene glycol, is collapsed in solutions with a highethanol/water ratio. Upon addition of water the polymer swells thusincreasing the polymers porosity. This volumetric change enables therelease of therapeutic compounds after contacting the polymer containingtherapeutic compounds with a mucus membrane. This exemplarymoisture-sensitive polymer is found in de las Heras Alarcon et al.,Chem. Soc. Rev. 34:276-285 (2005), which is hereby incorporated byreference in its entirety.

Exemplary moisture-sensitive polymers include copolymers of ionicmonomers, such asacrylamidopropane sulfonic acid sodium salt withneutral monomers, such as acrylamide; pH sensitive polymers, asdescribed above with high charge density; and grafted polymers, such aspolymethacrylic acid-graft-polyethylene glycol.

Solvent-Responsive or Chemical Exposure-Responsive Materials

Solvent-responsive materials can change their physical and chemicalproperties upon a change in the solvent or chemical content of thesurrounding medium or environment. Similar to the moisture-responsivematerials described above, solvent or chemical exposure-responsivematerials possess a transition involving an increasing or decreasingassociation with other components in the medium following exposure to asolvent or chemical. Generally, the solvent responds to displaces orincreases the volume of the existing medium, thus causing changesconsistent with the polymer's relative compatibility between the exposedsolvent and the existing medium. The solvent-responsive material can bea polymer composite with another material or a modified non-polymericmaterial.

En exemplary chemical-responsive material is a combination of activatedcarbon and polyaniline were formed into a composite structure orchemiresistive detector. Adsorption of biogenic amines causes a responsein the polymer component, which changes the resistance of the compositeand yields an electrical signal indicating the presence of the analyte.This exemplary solvent-sensitive polymer composite is found in patentnumber EP1278061B1, which is hereby incorporated by reference in itsentirety

Exemplary solvent or chemical exposure-responsive materials include apolymer/carbon blackcomposite, polyaniline/carbon black composite,gold/para-substituted thiophenol, gold clusters encapsulated withoctanethiol, and a dendrimer of poly(amidoamine).

Electric Field-Responsive Materials

Electric field-responsive materials can change their physical andchemical properties upon changes to the applied electric field. Theelectric field-responsive materials can be metal or a composite materialincluding a polymer and metal. In general, the electric field stimulatesa electric field sensitive component or electric “switch.” The polymercomponent of electric field-sensitive composites can be made from anypolymer with the desired polymer properties.

Electric field-responsive materials include those having one or more ofthe following switches: carbon black, carbon nanotube, metallic Nipowder, short carbon fibers (SCFs), or super-paramagnetic nanoparticles(e.g., magnetite nanoparticles). Electric field-responsive materials canoptionally include any composite or material described herein.

Magnetic Field-Responsive Materials

Magnetic field-responsive materials can change their physical propertiesupon changes to the applied magnetic field. The magneticfield-responsive materials can be metal or metal polymer compositematerials. In general, the magnetic field stimulates a magnetic fieldsensitive component or magnetic “switch.” The polymer component ofmagnetic field-sensitive composites can be made from any polymer withthe desired polymer properties.

Exemplary magnetic field-responsive materials or magnetic switchesinclude magnetite, poly[aniline-co-N-(1-butyric acid)]aniline/ironoxide, polylactide/nanocrystalline magnetite, maghemite, cobalt ferrite,carbonyl iron, ferromagnetic shape-memory alloy, magnetic nanoparticles(e.g., such as iron, cobalt, or iron oxide (e.g., Fe₃O₄)), spinelferrimagnets (e.g., such as CoFe₂O₄ and MnFe₂O₄), and alloys (e.g.,CoPt₃ and FePt). Exemplary polymers for magnetic field-responsivecomposites include any polymer described herein, e.g., high molecularweight polyacrylic acid, polyethylene glycol,poly(2-vinyl-N-methylpyridinium iodide), polystyrene, polyethyleneimine,and block copolymers of polystyrene, such aspoly(styrene-b-butadiene-b-styrene). Exemplary magnetic field-sensitivepolymers are found, e.g., in Dai et al., Chem. Soc. Rev. 39:4057-4066(2010), which is hereby incorporated by reference in its entirety.

Actuator-Embedded Materials

Actuator-embedded materials can include one or more microelectro-mechanical systems actuators (or MEMS actuators) to change theirphysical properties upon exposure to one or more stimuli. Suchactuator-embedded materials can result in mechanical, hydraulic, and/orpneumatic control of compression and/or expansion of the device. In someembodiments, the actuator-embedded materials include one or moreactuators in combination with one or more polymers (e.g., any describedherein, including polyvinylidenedifluoride, polyimide, polyester, rayon,epoxy, or combinations thereof). Exemplary actuators includes those madefrom one or more carbon nanotubes (e.g., single-walled carbon nanotubecomposites having a piezoelectric effect); one or more piezoceramicactuators (e.g., including lead magnesium niobate (PMN), and optionallyhaving one or more interdigitated electrodes, or one or morePb(Zr_(x)Ti₁,)O₃(PZT) materials (e.g., Ceramic B, PZT-2, PZT-4, PZT-5H,PZT-5A, PZT-4S, or PZT-8M, available from MTC Electro Ceramics,Berkshire, England)); one or more multilayered actuators (e.g., aPZT-based actuator, such as RAINBOW (Reduced And Internally Biased OxideWafer); a thin-layered piezoelectric composite material, such as THUNDER(Thin Layer Composite Unimorph ferroelectric DrivER and sensor); alaminate material including piezofibers, interdigitated electrodes, anda polymer (e.g., PVDF or polyimide, such as a Kapton® film), such as anAFC (Active Fiber Composite) developed by MIT University, USA; amacro-fiber composite including uniaxially aligned piezofibers in apolymer matrix, such as LaRC-MFC™ (NASA-Langley Research CenterMacro-Fiber Composite); or a composite actuator including a carbon fibercomposite layer with near-zero coefficient of thermal expansion (CTE), aPZT ceramic wafer, and a glass/epoxy layer, such as LIPCA (LightweightPiezo-Composite Actuator)); one or more optical fibers (e.g.,quartz-type and single-mode optical fibers, optionally embedded in anepoxy matrix); one or more piezopolymeric films; one or more piezoplates(e.g., a lead zirconate titanate plate that is optionally nickel-plated,e.g., PSI-5A4E or PSI-5H4E, available from Piezo Systems, Inc., Woburn,Mass.); one or more piezofibers (e.g., one or more carbon fibers and/orglass fibers, as well as composites thereof); one or more shape-memorypolymers (e.g., any described herein); or one or more shape-memoryalloys (e.g., any described herein, such as a NiTi alloy).

Exemplary actuator-embedded materials include carbon nanotubes incombination with polyvinylidenedifluoride (PVDF, optionally as amelt-blended or electrospun composite); carbon nanotubes in combinationwith polyimide (PI, optionally as a melt-blended or electrospuncomposite); unidirectional carbon fiber pre-impregnated sheets, such asXN-50A-RS3C, available from TenCate Corp., Nijverdal, Netherlands;Terfenol-D®, a magnetorestrictive material having terbium, iron, anddysprosium (available from Etrema Products Inc., Ames, Iowa); athermally actuated composite incombination with a microelectronicsubstrate, such as those described in U.S. Pat. No. 6,211,598, which ishereby incorporated by reference in its entirety; a composite materialincluding a nickel-tin shape-memory alloy (e.g., Nitinol™) in a thinfilm; or a magnetorestrictive composite including layers of Tb—Fe,polyimide, and Sm—Fe. Further exemplary materials are provided in U.S.Pat. No. 6,211,598 and International Pub. Nos. WO 2007/024038, each ofwhich is incorporated by reference in its entirety.

Unstretched Materials

The dressings of the invention can include one or more unstretchedmaterials. Such unstretched materials include those having sufficientrigidity to hinder stretching and those having one or more stretchablepolymers that are not stretched prior to affixing to a skin region.Exemplary unstretched materials include Tegaderm™, available from 3M,St. Paul, Minn., which can optionally be stretched after affixing to askin region.

Unstretched materials have not been dimensionally altered and are in astable dimensional state. Conversely, a stretched material has anunstable dimensional state because the material has been dimensionallyaltered within the material's elastic region by a force. An unstretchedmaterial can also be highly rigid or cross-linked (e.g., highlyresistant to stretching). Alternatively, an unstretched material can bea naïve material, which can be stretched in subsequent use.

Exemplary unstretched materials include any polymer or materialdescribed herein, a conventional material(s) (e.g., as describedherein), permanent adhesive(s), highly cross-linked polymericmaterial(s), and material(s) with high rigidity or hardness and lowductility (e.g., carboxymethylcellulose, gelatin, pectin, alginate,polyurethane, polymethacrylate, polyvinylpyrrolidone, nylon,polyethylene, polyacrylate, collagen, silicone, polyglycolicacid/polylactic acid, polyglycolic acid, polyglactin, benzylhyaluronate, or combinations thereof, in any useful form, such as afilm, bandage, gel, or hydrogel).

Adhesive Materials

An adhesive can be used within the dressing (e.g., as in the adhesivelayer) or used in combination with any method described herein topromote skin tightening.

The adhesive can be a pressure-sensitive adhesive (PSA). The propertiesof pressure sensitive adhesives are governed by three parameters, tack(initial adhesion), peel strength (adhesion), and shear strength(cohesion). Pressure-sensitive adhesives can be synthesized in severalways, including solvent-borne, water-borne, and hot-melt methods. Tackis the initial adhesion under slight pressure and short dwell time anddepends on the adhesive's ability to wet the contact surface. Peelstrength is the force required to remove the PSA from the contactsurface. The peel adhesion depends on many factors, including the tack,bonding history (e.g. force, dwell time), and adhesive composition.Shear strength is a measure of the adhesive's resistance to continuousstress. The shear strength is influenced by several parameters,including internal adhesion, cross-linking, and viscoelastic propertiesof the adhesive. Permanent adhesives are generally resistant todebonding and possess very high peel and shear strength.

Exemplary adhesives include a biocompatible matrix (e.g., thoseincluding at least one of collagen (e.g., a collagen sponge), lowmelting agarose (LMA), polylactic acid (PLA), and/or hyaluronicacid(e.g., hyaluranon); a photosensitizer (e.g., Rose Bengal,riboflavin-5-phosphate (R-5-P), methylene blue (MB),N-hydroxypyridine-2-(1H)-thione (N-HTP), a porphyrin, or a chlorin, aswell as precursors thereof); a photochemical agent (e.g., 1,8naphthalimide); a synthetic glue (e.g., a cyanoacrylate adhesive, apolyethylene glycol adhesive, or a gelatin-resorcinol-formaldehydeadhesive); or a biologic sealant (e.g., a mixture ofriboflavin-5-phosphate and fibrinogen, a fibrin-based sealant, analbumin-based sealant, or a starch-based sealant). In particularembodiments, the adhesive is biodegradable.

Exemplary pressure-sensitive adhesives include natural rubber, syntheticrubber (e.g., styrene-butadiene and styrene-ethylene copolymers),polyvinyl ether, polyurethane, acrylic, silicones, and ethylene-vinylacetate copolymers. A copolymer's adhesive properties can be altered byvarying the composition (via monomer components) changing the glasstransition temperature (Tg) or degree of cross-linking. In general, acopolymer with a lower Tg is less rigid and a copolymer with a higher Tgis more rigid. The tack of PSAs can be altered by the addition ofcomponents to alter the viscosity or mechanical properties. Exemplarypressure sensitive adhesives are described in Czech et al.,“Pressure-Sensitive Adhesives for Medical Applications,” in Wide Spectraof Quality Control, Dr. Isin Akyar (Ed., published by InTech), Chapter17 (2011), which is hereby incorporated by reference in its entirety

In one exemplary technique, a photosensitizer is applied to the tissue(e.g., Rose Bengal (RB) at concentration of less than 1.0% weight pervolume in a buffer, e.g., phosphate buffered saline to form a skintissue-RB complex), and then the tissue is irradiated withelectromagnetic energy to produce a seal (e.g., irradiated at awavelength of at least 488, at less than 2000 J/cm², and/or at less than1.5 W/cm², e.g., about 0.6 W/cm²). This exemplary technique is describedin U.S. Pat. No. 7,073,510, which is incorporated by reference in itsentirety. In another exemplary technique, a laser can be used for tissuewelding. In yet another exemplary technique, a photochemical agent isapplied to the tissue, and then the tissue is irradiated with visiblelight to produce a seal.

Therapeutic Agents

The dressings and methods of the invention can include one or moreuseful therapeutic agents. Exemplary agents include one or more growthfactors (e.g., vascular endothelial growth factor (VEGF),platelet-derived growth factor (PDGF), transforming growth factor beta(TGF-(3), fibroblast growth factor (FGF), epidermal growth factor (EGF),and keratinocyte growth factor); one or more stem cells (e.g., adiposetissue-derived stem cells and/or bone marrow-derived mesenchymal stemcells); steroids (for example, steroids to prevent edema), agents whichprevent post-inflammatory skin hyperpigmentation (e.g., hydroquinone,azelaic acid, kojic acid, mandelic acid, or niacinamide); one or moreanalgesics (e.g., paracetamol/acetaminophen, aspirin, a non-steroidalanti-inflammatory drug, as described herein, a cyclooxygenase-2-specificinhibitor, as described herein, dextropropoxyphene, co-codamol, anopioid (e.g., morphine, codeine, oxycodone, hydrocodone,dihydromorphine, pethidine, buprenorphine, tramadol, or methadone),fentanyl, procaine, lidocaine, tetracaine, dibucaine, benzocaine,p-butylaminobenzoic acid 2-(diethylamino) ethyl ester HCl, mepivacaine,piperocaine, dyclonine, or venlafaxine); one or more antibiotics (e.g.,cephalosporin, bactitracin, polymyxin B sulfate, neomycin, bismuthtribromophenate, or polysporin); one or more antifungals (e.g.,nystatin); one or more anti-inflammatory agents (e.g., a non-steroidalanti-inflammatory drug (NSAID, e.g., ibuprofen, ketoprofen,flurbiprofen, piroxicam, indomethacin, diclofenac, sulindac, naproxen,aspirin, ketorolac, or tacrolim us), a cyclooxygenase-2-specificinhibitor (COX-2 inhibitor, e.g., rofecoxib (Vioxx®), etoricoxib, andcelecoxib (Celebrex®)), a glucocorticoid agent, a specific cytokinedirected at T lymphocyte function), a steroid (e.g., a corticosteroid,such as a glucocorticoid (e.g., aldosterone, beclometasone,betamethasone, cortisone, deoxycorticosterone acetate, dexamethasone,fludrocortisone acetate, hydrocortisone, methylprednisolone, prednisone,prednisolone, or triamcinolone) or a mineralocorticoid agent (e.g.,aldosterone, corticosterone, or deoxycorticosterone)), or an immuneselective anti-inflammatory derivative (e.g.,phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG)));one or more antimicrobials (e.g., chlorhexidine gluconate, iodine (e.g.,tincture of iodine, povidone-iodine, or Lugol's iodine), or silver, suchas silver nitrate (e.g., as a 0.5% solution), silver sulfadiazine (e.g.,as a cream), or Ag+ in one or more useful carriers (e.g., an alginate,such as Acticoat® including nanocrystalline silver coating in highdensity polyethylene, available from Smith & Nephew, London, U.K., orSilvercel® including a mixture of alginate, carboxymethylcellulose, andsilver coated nylon fibers, available from Systagenix, Gatwick, U.K.; afoam (e.g., Contreet® Foam including a soft hydrophilic polyurethanefoam and silver, available from Coloplast A/S, Humlebaak, Denmark); ahydrocolloid (e.g., Aquacel® Ag including ionic silver and ahydrocolloid, available from Conva Tec Inc., Skillman, N.J.); or ahydrogel (e.g., Silvasorb® including ionic silver, available fromMedline Industries Inc., Mansfield, Mass.)); one or more antiseptics(e.g., an alcohol, such as ethanol (e.g., 60-90%), 1-propanol (e.g.,60-70%), as well as mixtures of 2-propanol/isopropanol; boric acid;calcium hypochlorite; hydrogen peroxide; manuka honey and/ormethylglyoxal; a phenol (carbolic acid) compound, e.g., sodium3,5-dibromo-4-hydroxybenzene sulfonate, trichlorophenylmethyliodosalicyl, or triclosan; a polyhexanide compound, e.g.,polyhexamethylene biguanide (PHMB); a quaternary ammonium compound, suchas benzalkonium chloride (BAC), benzethonium chloride (BZT), cetyltrimethylammonium bromide (CTMB), cetylpyridinium chloride (CPC),chlorhexidine (e.g., chlorhexidine gluconate), or octenidine (e.g.,octenidine dihydrochloride); sodium bicarbonate; sodium chloride; sodiumhypochlorite (e.g., optionally in combination with boric acid in Dakin'ssolution); or a triarylmethane dye (e.g., Brilliant Green)); one or moreantiproliferative agents (e.g., sirolimus, tacrolimus, zotarolimus,biolimus, or paclitaxel); one or more emollients; one or more hemostaticagents (e.g., collagen, such as microfibrillar collagen, chitosan,calcium-loaded zeolite, cellulose, anhydrous aluminum sulfate, silvernitrate, potassium alum, titanium oxide, fibrinogen, epinephrine,calcium alginate, poly-N-acetyl glucosamine, thrombin, coagulationfactor(s) (e.g., II, V, VII, VIII, IX, X, XI, XIII, or Von Willebrandfactor, as well as activated forms thereof), a procoagulant (e.g.,propyl gallate), an anti-fibrinolytic agent (e.g., epsilon aminocaproicacid or tranexamic acid), and the like); one or more procoagulativeagents (e.g., any hemostatic agent described herein, desmopressin,coagulation factor(s) (e.g., II, V, VII, VIII, IX, X, XI, XIII, or VonWillebrand factor, as well as activated forms thereof), procoagulants(e.g., propyl gallate), antifibrinolytics (e.g., epsilon aminocaproicacid), and the like); one or more anticoagulative agents (e.g., heparinor derivatives thereof, such as low molecular weight heparin,fondaparinux, oridraparinux; an anti-platelet agent, such as aspirin,dipyridamole, ticlopidine, clopidogrel, or prasugrel; a factor Xainhibitor, such as a direct factor Xa inhibitor, e.g., apixaban orrivaroxaban; a thrombin inhibitor, such as a direct thrombin inhibitor,e.g., argatroban, bivalirudin, dabigatran, hirudin, lepirudin, orximelagatran; or a coumarin derivative or vitamin K antagonist, such aswarfarin (coumadin), acenocoumarol, atromentin, phenindione, orphenprocoumon); one or more immune modulators, including corticosteroidsand non-steroidal immune modulators (e.g., NSAIDS, such as any describedherein); one or more proteins; or one or more vitamins (e.g., vitamin A,C, and/or E).

For the skin tightening methods described herein, the use ofanticoagulative and/or procoagulative agents may be of particularrelevance. For instance, by controlling the extent of bleeding and/orclotting in the incisions and/or excisions, the skin tightening effectcan be more effectively controlled. Thus, in some embodiments, themethods and devices herein include one or more anticoagulative agents,one or more procoagulative agents, one or more hemostatic agents, orcombinations thereof. In particular embodiments, the therapeutic agentcontrols the extent of bleeding and/or clotting in the treated skinregion, including the use one or more anticoagulative agents (e.g., toinhibit clot formation prior to skin healing or slit/hole closure)and/or one or more hemostatic or procoagulative agents.

Kits, Optionally Including One or More Applicators

Also described herein are kits for skin tightening or for treatingdiseases, disorders, and conditions that would benefit from skinrestoration or tightening. Accordingly, the present invention includeskits having one or more devices in combination with one or moreapplicators, as well kits having a combination of two or more devices,where at least one device is a tunable dressing as described herein.

The kit includes a device, such as any tunable dressing describedherein, and any other useful component. In some embodiments, the kitincludes a device (e.g., a tunable dressing) and an applicator. Theapplicator can include a frame or any structure configured to affix adevice to the skin region, where the frame or structure is optionallydisposable. In general, each device or tunable dressing is configured tobe affixed to a skin region, and the applicator can be configured toassist in the affixation of such a device. In some embodiments, theapplicator maintains the device in an unstretched state to allow foraffixing a device having an unstretched layer. In other embodiments, theapplicator holds the device to allow for aligning, positioning, and/orplacing the device on the desired skin region. In yet other embodiments,the applicator is configured to allow for affixing a tunable dressingimmediately after or shortly after forming one or more incisions orexcisions in the skin region. In such an embodiment, the applicator isconfigured to releasably attach to an apparatus for making such anincision or excision (e.g., an apparatus including one or more bladesand/or one or more tubes or a microablation tool, such as any describedherein). The applicator can be of any useful shape and/or material(e.g., any material or polymer described herein). In some embodiments,the applicator is a frame that provides sufficient support to the deviceor tunable dressing and/or provides a sterile method to affix the deviceor tunable dressing. In particular embodiments, the frame includes arigid plate having one or more view ports (e.g., one or more transparentwindows) to allow for positioning of the device. In some embodiments,the frame is structurally configured to attach to an apparatus formaking one or more incisions and/or excisions and to release a device(e.g., a tunable dressing) after making such an incision or excision.

In other embodiments, the applicator includes a liner layer having oneor more handles, where the liner layer is attached to the proximalsurface of a tunable dressing. The handles allow for positioning thedressing over the treated skin region. In some embodiments, the handlesare configured to be detached from the dressing immediately prior to orafter affixation. In some embodiments, the applicator includes areleasing layer. Exemplary applicators are provided in U.S. Pub. Nos.2012/0226306 and 2012/0226214, where each is hereby incorporated byreference in its entirety.

There may be a plurality of devices (e.g., tunable dressings) in a kit.Within the kit, the tunable dressings may be packaged individually(e.g., in sets of two or more). In some embodiments, each tunabledressing includes an applicator, where the dressing and the applicatorare configured together in one package. In other embodiments, the kitincludes one or more tunable dressings in combination with one or moreapplicators, where each of the dressing(s) and applicator(s) isindividually packaged. The dressing(s) and/or applicator(s) are packagedsuch that they remain sterile until use. In certain embodiments, thedressing(s) and/or applicator(s) are packaged in plastic sheaths.Further, to prevent contamination of the skin region, the dressing(s)and/or applicator(s) are preferably provided for as disposable and/orsingle-use items.

The kit can include a tunable dressing in combination with any otherdevice or apparatus described herein (e.g., a device or apparatus forforming one or more incisions or excisions in a skin region). In someembodiments, the other device or apparatus includes one or more bladesand/or one or more needles. In other embodiments, the other device orapparatus includes a microablation tool. Exemplary microablation toolsinclude a fractional laser microablation tool, a fractionalradiofrequency microablation tool, or a fractional ultrasonicmicroablation tool.

The kit can include any other useful components. Exemplary componentsinclude instructions on how to use the device(s), an air blower, a heatgun, a heating pad, one or more therapeutic agents (e.g., any describedherein, such as an anticoagulative and/or procoagulative agent, andoptionally in combination with a useful dispenser for applying thetherapeutic agent, such as a brush, spray, film, ointment, cream,lotion, or gel), one or more wound cleansers (e.g., including anyantibiotic, antimicrobial, or antiseptic, such as those describedherein, in any useful form, such as a brush, spray, film, ointment,cream, lotion, or gel), one or more debriding agents, and/or othersuitable or useful materials.

Methods for Treating Skin Regions

The present invention relates to methods and devices that can be appliedto treated skin regions. In particular embodiments, these regions aretreated with one or more procedures to improve skin appearance.Accordingly, the devices, dressings, and methods herein can be usefulfor skin rejuvenation (e.g., removal of pigment, tattoo removal, veins(e.g., spider veins or reticular veins), and/or vessels in the skin) orfor treating acne, allodynia, blemishes, ectopic dermatitis,hyperpigmentation, hyperplasia (e.g., lentigo or keratosis), loss oftranslucency, loss of elasticity, melasma (e.g., epidermal, dermal, ormixed subtypes), photodamage, rashes (e.g., erythematous, macular,papular, and/or bullous conditions), psoriasis, rhytides (or wrinkles,e.g., crow's feet, age-related rhytides, sun-related rhytides, orheredity-related rhytides), sallow color, scar contracture (e.g.,relaxation of scar tissue), scarring (e.g., due to acne, surgery, orother trauma), skin aging, skin contraction (e.g., excessive tension inthe skin), skin irritation/sensitivity, skin laxity (e.g., loose orsagging skin or other skin irregularities), striae (or stretch marks),vascular lesions (e.g., angioma, erythema, hemangioma, papule, port winestain, rosacea, reticular vein, or telangiectasia), or any otherunwanted skin irregularities.

Such treatments can be include any parts of the body, including the face(e.g., eyelid, cheeks, chin, forehead, lips, or nose), neck, chest(e.g., as in a breast lift), arms, legs, and/or back. Accordingly, thedevices on the invention can be arranged or configured to be amenable tothe size or geometry of different body regions. Such arrangements andconfigurations can include any useful shape (e.g., linear, curved, orstellate), size, and/or depth.

In one exemplary procedure, a plurality of tissue portions are incisedinto or excised from a skin region in a subject (e.g., about 2, 3, 4, 5,6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, or more tissueportions, such as between about 2 and 100 tissue portions (e.g., between2 and 10, 2 and 15, 2 and 20, 2 and 25, 2 and 30, 2 and 35, 2 and 40, 2and 45, 2 and 50, 2 and 75, 5 and 10, 5 and 15, 5 and 20, 5 and 25, 5and 30, 5 and 35, 5 and 40, 5 and 45, 5 and 50, 5 and 75, 5 and 100, 10and 20, 10 and 25, 10 and 30, 10 and 35, 10 and 40, 10 and 45, 10 and50, 10 and 75, 10 and 100, 15 and 20, 15 and 25, 15 and 30, 15 and 35,15 and 40, 15 and 45, 15 and 50, 15 and 75, 15 and 100, 20 and 25, 20and 30, 20 and 35, 20 and 40, 20 and 45, 20 and 50, 20 and 75, 20 and100, 25 and 30, 25 and 35, 25 and 40, 25 and 45, 25 and 50, 25 and 75,25 and 100, 30 and 35, 30 and 40, 30 and 45, 30 and 50, 30 and 75, 30and 100, 35 and 40, 35 and 45, 35 and 50, 35 and 75, 35 and 100, 40 and45, 40 and 50, 40 and 75, 40 and 100, 50 and 75, or 50 and 100)). Suchtissue portions can be included in any useful geometric, non-geometric,or random array (e.g., such as those described herein for an array oftubes and/or blades). Such tissue portions can have any useful dimensionthat promotes wound or skin healing. Non-limiting dimensions of a tissueportion includes at least one dimension that is less than about 2.0 mm(e.g., less than or equal to about 1.5 mm, 1 mm, 0.75 mm, 0.5 mm, 0.3mm, 0.2 mm, 0.1 mm, 0.075 mm, 0.05 mm, or 0.025 mm) or between about0.025 mm and 2.0 mm (e.g., between about 0.025 mm and 1.5 mm, 0.025 mmand 1.0 mm, 0.025 mm and 0.75 mm, 0.025 mm and 0.5 mm, 0.025 mm and 0.3mm, 0.025 mm and 0.2 mm, 0.025 mm and 0.1 mm, 0.025 mm and 0.075 mm,0.025 mm and 0.05 mm, 0.05 mm and 2.0 mm, 0.05 mm and 1.5 mm, 0.05 mmand 1.0 mm, 0.05 mm and 0.75 mm, 0.05 mm and 0.5 mm, 0.05 mm and 0.3 mm,0.05 mm and 0.2 mm, 0.05 mm and 0.1 mm, 0.05 mm and 0.075 mm, 0.075 mmand 2.0 mm, 0.075 mm and 1.5 mm, 0.075 mm and 1.0 mm, 0.075 mm and 0.75mm, 0.075 mm and 0.5 mm, 0.075 mm and 0.3 mm, 0.075 mm and 0.2 mm, 0.075mm and 0.1 mm, 0.1 mm and 2.0 mm, 0.1 mm and 1.5 mm, 0.1 mm and 1.0 mm,0.1 mm and 0.75 mm, 0.1 mm and 0.5 mm, 0.1 mm and 0.3 mm, 0.1 mm and 0.2mm, 0.2 mm and 2.0 mm, 0.2 mm and 1.5 mm, 0.2 mm and 1.0 mm, 0.2 mm and0.75 mm, 0.2 mm and 0.5 mm, 0.2 mm and 0.3 mm, 0.3 mm and 2.0 mm, 0.3 mmand 1.5 mm, 0.3 mm and 1.0 mm, 0.3 mm and 0.75 mm, 0.3 mm and 0.5 mm,0.5 mm and 2.0 mm, 0.5 mm and 1.5 mm, 0.5 mm and 1.0 mm, 0.5 mm and 0.75mm, 0.75 mm and 2.0 mm, 0.75 mm and 1.5 mm, or 0.75 mm and 1.0 mm).

In some embodiments, the incised or excised tissue portions forms a holein the skin region, where the diameter or width of the hole is less thanabout 1.0 mm and results in a tissue portion having a diameter or widththat is less than about 1.0 mm. In further embodiments, the tissueportion has a diameter or width that is less than about 1.0 mm and alength of more than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm.2.5 mm, 3.0 mm, or 3.5 mm). In particular embodiments, relatively smalldimensions of the tissue portions can promote healing while minimizingthe formation of scars.

In other embodiments, the incised or excised tissue portions forms aslit in the skin region, where the length or width of the slit is lessthan about 1.0 mm and results in a tissue portion having a length orwidth that is less than about 1.0 mm. In further embodiments, the tissueportion has a length or width that is less than about 1.0 mm and alength of more than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm.2.5 mm, 3.0 mm, or 3.5 mm). In particular embodiments, relatively smalldimensions of the tissue portions can promote healing while minimizingthe formation of scars.

The tissue portion can be of any useful shape. Exemplary shapes includecylinders (i.e., thereby forming round or elongated holes in the skinregion), holes (e.g., microholes), slits (e.g., microslits), elongatedstrips (i.e., thereby forming elongated openings in the skin region), orother geometries including at least dimension that is less than about1.0 mm (e.g., less than or equal to about 0.75 mm, about 0.5 mm, about0.3 mm, about 0.2 mm, about 0.1 mm, or about 0.05 mm) or between about0.05 mm and 1.0 mm (e.g., 0.05 mm and 0.75 mm, 0.05 mm and 0.5 mm, 0.05mm and 0.3 mm, 0.05 mm and 0.2 mm, 0.05 mm and 0.1 mm, 0.1 mm and 1.0mm, 0.1 mm and 0.75 mm, 0.1 mm and 0.5 mm, 0.1 mm and 0.3 mm, 0.1 mm and0.2 mm, 0.2 mm and 1.0 mm, 0.2 mm and 0.75 mm, 0.2 mm and 0.5 mm, 0.2 mmand 0.3 mm, 0.3 mm and 1.0 mm, 0.3 mm and 0.75 mm, 0.3 mm and 0.5 mm,0.4 mm and 1.0 mm, 0.4 mm and 0.75 mm, 0.4 mm and 0.5 mm, 0.5 mm and 1.0mm, 0.5 mm and 0.75 mm, 0.6 mm and 1.0 mm, 0.6 mm and 0.75 mm, or 0.75mm and 1.0 mm). In other embodiments, the incised tissue portion and/orexcised tissue portion has an areal dimension (e.g., a cross-sectionaldimension in the xy-plane, such as an areal dimension of a circle ornon-circular (e.g., elliptical) shape) of less than about or equal toabout 1.0 mm² (e.g., less than or equal to about 0.9 mm², 0.8 mm², 0.7mm², 0.6 mm², 0.5 mm², 0.4 mm², 0.3 mm², 0.2 mm², 0.1 mm², 0.07 mm²,0.05 mm², 0.03 mm², 0.02 mm², 0.01 mm², 0.007 mm², 0.005 mm², 0.003 mm²,0.002 mm², or 0.001 mm²) or between about 0.001 mm² and 1.0 mm² (e.g.,0.001 mm² and 0.9 mm², 0.001 mm² and 0.8 mm², 0.001 mm² and 0.7 mm²,0.001 mm² and 0.6 mm², 0.001 mm² and 0.5 mm², 0.001 mm² and 0.4 mm²,0.001 mm² and 0.3 mm², 0.001 mm² and 0.2 mm², 0.001 mm² and 0.1 mm²,0.001 mm² and 0.07 mm², 0.001 mm² and 0.05 mm², 0.001 mm² and 0.03 mm²,0.001 mm² and 0.02 mm², 0.001 mm² and 0.01 mm², 0.001 mm² and 0.007 mm²,0.001 mm² and 0.005 mm², 0.001 mm² and 0.003 mm², 0.001 mm² and 0.002mm², 0.002 mm² and 1.0 mm², 0.002 mm² and 0.9 mm², 0.002 mm² and 0.8mm², 0.002 mm² and 0.7 mm², 0.002 mm² and 0.6 mm², 0.002 mm² and 0.5mm², 0.002 mm² and 0.4 mm², 0.002 mm² and 0.3 mm², 0.002 mm² and 0.2mm², 0.002 mm² and 0.1 mm², 0.002 mm² and 0.07 mm², 0.002 mm² and 0.05mm², 0.002 mm² and 0.03 mm², 0.002 mm² and 0.02 mm², 0.002 mm² and 0.01mm², 0.002 mm² and 0.007 mm², 0.002 mm² and 0.005 mm², 0.002 mm² and0.003 mm², 0.005 mm² and 1.0 mm², 0.005 mm² and 0.9 mm², 0.005 mm² and0.8 mm², 0.005 mm2 and 0.7 mm², 0.005 mm² and 0.6 mm², 0.005 mm² and 0.5mm², 0.005 mm² and 0.4 mm², 0.005 mm² and 0.3 mm², 0.005 mm² and 0.2mm², 0.005 mm² and 0.1 mm², 0.005 mm² and 0.07 mm², 0.005 mm² and 0.05mm², 0.005 mm² and 0.03 mm², 0.005 mm² and 0.02 mm², 0.005 mm² and 0.01mm², 0.005 mm² and 0.007 mm², 0.007 mm² and 1.0 mm², 0.007 mm² and 0.9mm², 0.007 mm² and 0.8 mm², 0.007 mm² and 0.7 mm², 0.007 mm² and 0.6mm², 0.007 mm² and 0.5 mm², 0.007 mm² and 0.4 mm², 0.007 mm² and 0.3mm², 0.007 mm² and 0.2 mm², 0.007 mm² and 0.1 mm², 0.007 mm² and 0.07mm², 0.007 mm² and 0.05 mm², 0.007 mm² and 0.03 mm², 0.007 mm² and 0.02mm², 0.007 mm² and 0.01 mm², 0.01 mm² and 1.0 mm², 0.01 mm² and 0.9 mm²,0.01 mm² and 0.8 mm², 0.01 mm² and 0.7 mm², 0.01 mm² and 0.6 mm², 0.01mm² and 0.5 mm², 0.01 mm² and 0.4 mm², 0.01 mm² and 0.3 mm², 0.01 mm²and 0.2 mm², 0.01 mm² and 0.1 mm², 0.01 mm² and 0.07 mm², 0.01 mm² and0.05 mm², 0.01 mm² and 0.03 mm², 0.01 mm² and 0.02 mm², 0.03 mm² and 1.0mm², 0.03 mm² and 0.9 mm², 0.03 mm² and 0.8 mm², 0.03 mm² and 0.7 mm²,0.03 mm² and 0.6 mm², 0.03 mm² and 0.5 mm², 0.03 mm² and 0.4 mm², 0.03mm² and 0.3 mm², 0.03 mm² and 0.2 mm², 0.03 mm² and 0.1 mm², 0.03 mm²and 0.07 mm², 0.03 mm² and 0.05 mm², 0.07 mm² and 1.0 mm², 0.07 mm² and0.9 mm², 0.07 mm² and 0.8 mm², 0.07 mm² and 0.7 mm², 0.07 mm² and 0.6mm², 0.07 mm² and 0.5 mm², 0.07 mm² and 0.4 mm², 0.07 mm² and 0.3 mm²,0.07 mm² and 0.2 mm², 0.07 mm² and 0.1 mm², 0.1 mm² and 1.0 mm², 0.1 mm²and 0.9 mm², 0.1 mm² and 0.8 mm², 0.1 mm² and 0.7 mm², 0.1 mm² and 0.6mm², 0.1 mm² and 0.5 mm², 0.1 mm² and 0.4 mm², 0.1 mm² and 0.3 mm², 0.1mm² and 0.2 mm², 0.3 mm² and 1.0 mm², 0.3 mm² and 0.9 mm², 0.3 mm² and0.8 mm², 0.3 mm² and 0.7 mm², 0.3 mm² and 0.6 mm², 0.3 mm² and 0.5 mm²,0.3 mm² and 0.4 mm², 0.5 mm² and 1.0 mm², 0.5 mm² and 0.9 mm², 0.5 mm²and 0.8 mm², 0.5 mm² and 0.7 mm², 0.5 mm² and 0.6 mm², 0.7 mm² and 1.0mm², 0.7 mm² and 0.9 mm², or 0.7 mm² and 0.8 mm²). When viewed from thetop of the skin (i.e., along the z-direction, as shown in FIG. 1A, orwithin the xy-plane of the skin, as shown in FIGS. 3A-3C), the shape ofthe hole can be circular or non-circular (e.g., elliptical). Exemplaryshapes of tissue portions are provided in FIGS. 1A-1C and 3A-3C and itsassociated text of U.S. Pub. No. 2012/0041430, which are herebyincorporated by reference in its entirety

Any beneficial areal fraction of the skin region can be removed, such asan areal fraction of less than about 70% (e.g., less than about 65%,60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 10%, or 5%) or such asbetween about 5% and 80% (e.g., between about 5% and 10%, 5% and 10%, 5%and 20%, 5% and 25%, 5% and 30%, 5% and 35%, 5% and 40%, 5% and 45%, 5%and 50%, 5% and 55%, 5% and 60%, 5% and 65%, 5% and 70%, 5% and 75%, 10%and 10%, 10% and 20%, 10% and 25%, 10% and 30%, 10% and 35%, 10% and40%, 10% and 45%, 10% and 50%, 10% and 55%, 10% and 60%, 10% and 65%,10% and 70%, 10% and 75%, 10% and 80%, 15% and 20%, 15% and 25%, 15% and30%, 15% and 35%, 15% and 40%, 15% and 45%, 15% and 50%, 15% and 55%,15% and 60%, 15% and 65%, 15% and 70%, 15% and 75%, 15% and 80%, 20% and25%, 20% and 30%, 20% and 35%, 20% and 40%, 20% and 45%, 20% and 50%,20% and 55%, 20% and 60%, 20% and 65%, 20% and 70%, 20% and 75%, or 20%and 80%).

Furthermore, the plurality of tissue portions can be incised or excisedin any beneficial pattern within the skin region. Exemplary patternswithin the skin region include tile patterns or fractal-like shapes,where the array of hollow tubes can be arranged, e.g., in a base, toeffectuate such a pattern. For example, a higher density and/or smallerspacing of tissue portions (e.g., slits and/or holes) can be incised orexcised in the skin in center of the pattern or in thicker portions ofthe skin. In another example, the pattern within the skin can be random,staggered rows, parallel rows, a circular pattern, a spiral pattern, asquare or rectangular pattern, a triangular pattern, a hexagonalpattern, a radial distribution, or a combination of one or more suchpatterns of the incised or excised tissue portions. The pattern canarise from modifications to the average length, depth, or width of anincised or excised tissue portion, as well as the density, orientation,and spacing between such incisions and/or excisions (e.g., by using anapparatus having one or more blades or tubes with differing lengths,widths, or geometries that are arranged in a particular density orspacing pattern). Such patterns can be optimized to promoteunidirectional, non-directional, or multidirectional contraction orexpansion of skin (e.g., in the x-direction, y-direction, x-direction,x-y plane, y-z plane, x-z plane, and/or xyz-plane), such as by modifyingthe average length, depth, width, density, orientation, and/or spacingbetween incisions and/or excisions.

Any useful portion of the skin can be incised or excised. Such tissueportions can include epidermal tissue, dermal tissue, and/or cells ortissue proximal to the dermal/fatty layer boundary (e.g., stem cells).In particular embodiments, the incised or excised tissue portions formsa hole in the skin region, where the depth of the hole is more thanabout 1.0 mm and results in a tissue portion having a length that ismore than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5 mm, 3.0mm, or 3.5 mm). In particular embodiments, the incised or excised tissueportions forms a slit in the skin region, where the depth of the slit ismore than about 1.0 mm and results in a tissue portion having a lengththat is more than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5mm, 3.0 mm, or 3.5 mm). In some embodiments, the tissue portion has alength that corresponds to a typical total depth of the skin layer(e.g., epidermal and dermal layers). Based on the part of the body, thetotal depth of the epidermal and dermal layers can vary. In someembodiments, the depth of the epidermal layer is between about 0.8 mm to1.4 mm, and/or the depth of the dermal layer is between about 0.3 mm to4.0 mm. In other embodiments, the total depth of the skin layer (e.g.,epidermal and dermal layers) is between about 1.0 mm and 5.5 mm, therebyresulting in a tissue portion having a length between about 1.0 mm and5.5 mm (e.g., between about 1.0 mm and 1.5 mm, 1.0 mm and 2.0 mm, 1.0 mmand 2.5 mm, 1.0 mm and 3.0 mm, 1.0 mm and 3.5 mm, 1.0 mm and 4.0 mm, 1.0mm and 4.5 mm, 1.0 mm and 5.0 mm, 1.5 mm and 2.0 mm, 1.5 mm and 2.5 mm,1.5 mm and 3.0 mm, 1.5 mm and 3.5 mm, 1.5 mm and 4.0 mm, 1.5 mm and 4.5mm, 1.5 mm and 5.0 mm, 1.5 mm and 5.5 mm, 2.0 mm and 2.5 mm, 2.0 mm and3.0 mm, 2.0 mm and 3.5 mm, 2.0 mm and 4.0 mm, 2.0 mm and 4.5 mm, 2.0 mmand 5.0 mm, 2.0 and 5.5 mm, 2.5 mm and 3.0 mm, 2.5 mm and 3.5 mm, 2.5 mmand 4.0 mm, 2.5 mm and 4.5 mm, 2.5 mm and 5.0 mm, 2.5 mm and 5.5 mm, 3.0mm and 3.5 mm, 3.0 mm and 4.0 mm, 3.0 mm and 4.5 mm, 3.0 mm and 5.0 mm,3.0 and 5.5 mm, 3.5 mm and 4.0 mm, 3.5 mm and 4.5 mm, 3.5 mm and 5.0 mm,3.5 and 5.5 mm, 4.0 mm and 4.5 mm, 4.0 mm and 5.0 mm, 4.0 and 5.5 mm,4.5 mm and 5.0 mm, 4.5 and 5.5 mm, or 5.0 mm and 5.5 mm). In yet otherembodiments, the average total depth of the tissue portion or the skinlayer (e.g., epidermal and dermal layers) is about 1.5 mm. In yet otherembodiments, the average total depth of the tissue portion or the skinlayer (e.g., epidermal and dermal layers) is about 3 mm. In furtherembodiments, the tissue portion does not include a significant amount ofsubcutaneous tissue, and any apparatus described herein can be optimized(e.g., with one or more stop arrangements) to control the depth of theincision or excision and/or the length of the incised or excised tissueportions.

Incisions can be performed by any useful procedure or component. Forexample, a plurality of incised tissue portions can be achieved by useof an ablative laser (e.g., an ablative CO₂ laser (about 10600 nm), asuperficial fractional CO₂ laser, a fractional Er:YAG laser (about 2940nm), a fractional Er:YSGG laser (about 2790 nm), an Nd-YAG laser (about1320 nm), a mid-IR fractional photothermolysis laser, or a fractionaldeep dermal ablation CO₂ laser), an ultrasonic apparatus, a non-coherentlight source, a radiofrequency source, or a plurality of blades (e.g.,substantially parallel blades). In some embodiments, the one or moreblades can include connected, adjacent blades to provide narrow,elongated openings (or slits) in the skin region. Exemplary proceduresand apparatuses including one or more blades are described in FIGS. 3,4, 5A-5B, 6A-6B, 7A-7C, 8A-8C, 9, 10, 11A-11B, 14, 15A-15B, and 16A-16Dand its associated text in U.S. Pub. No. 2011/0251602, which areincorporated herein by reference.

Excisions can be performed by any useful procedure or component. Forexample, a plurality of excised tissue portions can be achieved by useof one or more hollow tubes or needles (e.g., where the inner diameterof at least one tube is less than about 0.5 mm, about 0.3 mm, or about0.2 mm) or one or more solid tubes or needles. Exemplary components forperforming excisions include a needle (e.g., a 16 gauge needle having aninner diameter of 1.194 mm; an 18 gauge needle having an inner diameterof 0.838 mm; a 20 gauge needle having an inner diameter of 0.564 mm; a23 gauge needle having an inner diameter of about 0.337 mm and an outerdiameter of about 0.51 mm, thereby resulting in a tissue portion havinga dimension (e.g., a width or diameter) of about 0.3 mm; a 25 gaugeneedle having an inner diameter of about 0.26 mm or a thin-walled 25gauge needle having an inner diameter of about 0.31 mm and an outerdiameter of about 0.51 mm, thereby resulting in a tissue portion havinga dimension (e.g., a width or diameter) of about 0.2 mm; a 30 gaugeneedle having an inner diameter of about 0.159 mm; a 32 gauge needlehaving an inner diameter of about 0.108 mm; or a 34 gauge needle havingan inner diameter of about 0.0826 mm), where such needles can be ahollow biopsy needle or a solid needle; one or more microaugers; or oneor more microabraders.

The geometry of the one or more tubes can include at least two points(or prongs) (e.g., at least three, four, five, six, seven, eight, ormore points) provided at a distal end of the tube (e.g., to facilitateseparation of the tissue portions from the surrounding tissue and/orinsertion of the tubes into the skin region), where an angle formed byat least one of the points is about thirty degrees. Exemplary tubesinclude those having two points (e.g., by grinding in orientations thatare 180 degrees apart), three points (e.g., by grinding in orientationsthat are 120 degrees apart), or four points (e.g., by grinding inorientations that are 90 degrees apart). The points can optionallyinclude a beveled edge (e.g., to further facilitate separation of tissueportions or insertion of tubes).

The points can have any useful geometric configuration. In one example,the tube has a longitudinal axis (i.e., along the length of the tube)and a diameter (i.e., through the cross-section of the tube), as well asa proximal end and the distal end. The distal end can include one ormore points, where each point is characterized by angle a (i.e., theangle between each of the opposing lateral sides of the tube that formsthe point and the longitudinal axis of the tube). When viewed from theside, the angle formed by a point is characterized by angle 2 a. Forexample, a tip angle of about 30 degrees corresponds to an angle a ofabout 15 degrees. Furthermore, the angled distal end of the tube can beformed (e.g., by grinding or cutting) at angle a, e.g., to form a secondbevel structure at the distal end of a tube, where this second bevel ischaracterized by angle r3 and is orthogonal to the primary point (orbevel) characterized by angle a. This second bevel can be provided toreduce the size or width of the point. Exemplary angle a and p includesless than about 20 degrees, 15 degrees, 10, degrees, or 5 degrees (e.g.,about 15 degrees, 10 degrees, 6 degrees, 5 degrees, or 3 degrees). See,e.g., FIGS. 8A-8J and its associated text of U.S. Pub. No. 2011/0313429,which are hereby incorporated by reference in its entirety, forexemplary points, angle a, and angle [3.

The tubes can optionally include one or more notches within the lumen ofthe needle (i.e., if the tube is hollow) and/or extensions on theexterior surface of the needle (e.g., at the distal portion of theneedle). Such notches and extensions could be useful to promote cuttingof tissue surrounding the incised or excised tissue portions. Exemplaryneedles having such notches and/or extensions include a microauger, aswell as any needles provided in FIGS. 5A-5E and described its associatedtext of International Pub. No. WO 2012/103492, which are herebyincorporated by reference in its entirety, for apparatuses havingnotches and/or extensions.

The tubes can optionally include one or more protrusions or barbs withinthe lumen of the needle (i.e., if the tube is hollow) to promoteretention of fat within the needle. In use, an apparatus including suchtubes can be inserted into the subcutaneous fat layer and then withdrawnto remove retained fat tissue. See, e.g., FIGS. 1A-1C, 2A-2C, 3A, 4,5A-5C, 6A-6B, 7, and 8A-8C and its associated text of International Pub.No. WO 2013/013196, which are hereby incorporated by reference in itsentirety, for apparatuses having protrusions or barbs.

The components for making incisions and/or excisions (e.g., bladesand/or tubes) can be provided in any useful arrangement (e.g., a lineararray, a radial array, or any described herein) of one or morecomponents (e.g., two, three, four, five, ten, thirty, fifty, hundred,or more). The spacing between each component (e.g., blade and/or tube)can be of any useful dimension, such as between about 1 mm and 50 mm(e.g., between about 1 mm and 40 mm, 1 mm and 30 mm, 1 mm and 25 mm, 1mm and 20 mm, 1 mm and 15 mm, 1 mm and 10 mm, 1 mm and 5 mm, 1 mm and 3mm, 3 mm and 50 mm, 3 mm and 40 mm, 3 mm and 30 mm, 3 mm and 25 mm, 3 mmand 20 mm, 3 mm and 15 mm, 3 mm and 10 mm, 3 mm and 5 mm, 5 mm and 50mm, 5 mm and 40 mm, 5 mm and 30 mm, 5 mm and 25 mm, 5 mm and 20 mm, 5 mmand 15 mm, 5 mm and 10 mm, 10 mm and 50 mm, 10 mm and 40 mm, 10 mm and30 mm, 10 mm and 25 mm, 10 mm and 20 mm, 10 mm and 15 mm, 15 mm and 50mm, 15 mm and 40 mm, 15 mm and 30 mm, 15 mm and 25 mm, 15 mm and 20 mm,20 mm and 50 mm, 20 mm and 40 mm, 20 mm and 30 mm, 20 mm and 25 mm, 30mm and 50 mm, 30 mm and 40 mm, or 40 mm and 50 mm). Such arrangementscan include one or more tubes and/or blades (e.g., about 2, 3, 4, 5, 6,7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, or more tubesand/or blades, such as between about 2 and 100 tubes and/or blades(e.g., between 2 and 10, 2 and 15, 2 and 20, 2 and 25, 2 and 30, 2 and35, 2 and 40, 2 and 45, 2 and 50, 2 and 75, 5 and 10, 5 and 15, 5 and20, 5 and 25, 5 and 30, 5 and 35, 5 and 40, 5 and 45, 5 and 50, 5 and75, 5 and 100, 10 and 20, 10 and 25, 10 and 30, 10 and 35, 10 and 40, 10and 45, 10 and 50, 10 and 75, 10 and 100, 15 and 20, 15 and 25, 15 and30, 15 and 35, 15 and 40, 15 and 45, 15 and 50, 15 and 75, 15 and 100,20 and 25, 20 and 30, 20 and 35, 20 and 40, 20 and 45, 20 and 50, 20 and75, 20 and 100, 25 and 30, 25 and 35, 25 and 40, 25 and 45, 25 and 50,25 and 75, 25 and 100, 30 and 35, 30 and 40, 30 and 45, 30 and 50, 30and 75, 30 and 100, 35 and 40, 35 and 45, 35 and 50, 35 and 75, 35 and100, 40 and 45, 40 and 50, 40 and 75, 40 and 100, 50 and 75, or 50 and100)).

Such arrangements of components can be any of various two-dimensional orthree-dimensional patterns along a base holding one or more componentsfor making incisions and/or excisions (e.g., blades and/or tubes). Thebase can be optionally mounted on a roller apparatus having acylindrical body with a longitudinal rotational axis, where the one ormore blades and/or tubes are arranged on the longitudinal surface of thecylindrical body. In some embodiments, the blade or tube extends assubstantially coplanar extensions of the cylindrical body. In use,rotation of the cylindrical body along the skin results in the incisionor excision of tissue portions by the blade or tubes. Exemplary rollerapparatuses are provided in FIGS. 11A-11B and its associated text inU.S. Pub. No. 2011/0251602, in FIGS. 3A-3B and its associated text inInternational Pub. No. WO 2012/103492, which are hereby incorporated byreference in its entirety.

Such components for making incisions and/or excisions (e.g., bladesand/or tubes) can include one or more stop arrangements (e.g., one ormore collars, which can be coupled to the blade to allow for adjustmentalong the long axis of the blade or which can be coupled to the outerportion of the tube and be adjusted along the long axis of the tube tocontrol the depth of incision or excision in the biological tissue); oneor more sleeves around a portion of a blade and/or a tube, such that thesleeve is slidably translatable along the longitudinal axis of the tubeor blade (e.g., to incise or excise tissue portions below the surface ofthe skin region); a vibrating arrangement (e.g., a piezoelectricelement, a solenoid, a pneumatic element, or a hydraulic element) thatmechanically couples to at least one blade or hollow tube (e.g., topromote insertion of one or more blades or tubes into the skin region,such as by providing an amplitude of vibration in the range of about50-500 pm (e.g., between about 100-200 pm) or by providing a frequencyof the induced vibrations to be between about 10 Hz and about 10 kHz(e.g., between about 500 Hz and about 2 kHz, or even about 1 kHz)); asuction or pressure system (e.g., by squeezing a flexible bulb ordeformable membrane attached thereto or by opening a valve leading froma source of elevated pressure, such as a small pump) to stabilize thesurrounding skin region prior to incision or excision and/or tofacilitate removal of the skin portions from the tube; a pin within thelumen to the tube to facilitate removal of the skin portions from thetube; one or more actuators for positioning, translating, and/orrotating the one or more blades and/or tubes relative to the skinportion or relative to the optional one or more pins; a housing or frameto stabilize the surrounding skin region prior to incision or excision;one or more actuators for positioning and/or translating the one or morepins relative to the skin portion or relative to one or more tubes; oneor more sensors (e.g., force sensors, optical sensors, laser fibers,photodetectors, and/or position sensors) in communication with one ormore tubes, blades, pins, actuators, valves, or pressure systems todetect the position of the tubes or pins, the presence of a tissueportion in the tube, the position of the apparatus relative to thetreated skin portion; a reciprocating arrangement attached to a base ora substrate having one or more attached blades or tubes (e.g., a motoror actuator configured to repeatedly insert and/or withdrawn one or moreblades or tubes); a fluid system coupled to the blades and/or tubes tofacilitate removal of incised or excised tissue portions or to irrigatethe skin portion, e.g., with saline or a phosphate buffered solution; aheat source (e.g., a resistive heater or current) in communication withthe blade and/or tube to promote cauterization or ablation of tissueportions; an optical element (e.g., a lens, a prism, a reflector, etc.)to facilitate viewing of the skin portion beneath the apparatus, tube,or blade; and/or an abrading element optionally mounted on a rotatingshaft (e.g., to promote dermabrasion).

Exemplary blades, tubes, pins, apparatuses, and methods are provided inFIGS. 5A-5B, 6A-6C, 7, and 8A-8B and its associated text of U.S. Pub.No. 2012/0041430; in FIGS. 8A-8J, 10A-10B, 11, 12, 13A-13B, 14, and15A-15E and its associated text of U.S. Pub. No. 2011/0313429; in FIGS.3, 4, 5A-5B, 6A-6B, 7A-7C, 8A-8C, 9, 10, 11A-11B, 14, 15A-15B, and 16A-Dand its associated text in U.S. Pub. No. 2011/0251602; in FIGS. 1A-1B,2A-2C, 3A-3B, 4A-4B, 5A-5E, and 6 and its associated text inInternational Pub. No. WO 2012/103492; in FIGS. 1, 2, 3, and 4 and itsassociated text in International Pub. No. WO 2012/103483; in FIGS. 1, 3,and 4 and its associated text in International Pub. No. WO 2012/103488;in FIGS. 1A-1C, 2A-2C, 3A, 4, 5A-5C, 6A-6B, 7, and 8A-8C and itsassociated text of International Pub. No. WO 2013/013196; in FIGS. 1,2A-2D, 3, and 4 and its associated text of International Pub. No. WO2013/013199, which are hereby incorporated by reference in its entirety.

The tubes, blades, pins, and apparatuses can be formed from any usefulmaterial and optionally coated or chemically treated to promote incisionor excision of a tissue portion and/or to increase precision oreffectiveness for treating the skin region. Exemplary materials includemetal (e.g., a stainless steel tube, 304 stainless steel, a surgicalstainless steel), a biopsy needle, an epoxy, a glass, a polymer, aplastic, a resin, another structurally rigid material, or a similarstructure. Exemplary coatings include a lubricant, a low-frictionmaterial (e.g., Teflon™), a chromium coating (e.g., ME-92TM, such as toincrease material strength), a plastic, a polymer (e.g., nylon orpolyethylene), a polished metal alloy, or the like.

In particular embodiments, an apparatus for treating skin includes atleast one hollow tube including at least two points provided at a distalend thereof and an optional stop arrangement coupled to the outerportion of the tube (e.g., to control and/or limit a distance to whichthe one tube is inserted into a biological tissue), where the angleformed by at least one of the points is about thirty degrees, where theinner diameter of at least one tube is less than about 1 mm, and whereat least one section of the hollow tube is structured to be insertedinto a biological tissue to incise or excise at least one tissuetherefrom when the tube is withdrawn from the tissue. In otherembodiments, the apparatus further includes a pin provided at leastpartially within the central lumen of a tube, where the pin iscontrollably translatable in a direction along a longitudinal axis ofthe one tube and the pin is configured to facilitate removal of at leastone tissue portion from the tube. In another embodiment, the apparatusfor treating skin includes a plurality of cutting arrangements (e.g.,blades) structured to form a plurality of spaced-apart micro-slits(e.g., openings) in tissue, where each of the micro-slits has a lengthof extension along a surface of the tissue that is less than about 2 mm.In other embodiments, the apparatus includes at least one hollow tube(e.g., needle) configured to be at least partially inserted into abiological tissue; at least one opening provided on a wall of the hollowtube; at least one cutting edge protruding from the wall of the hollowtube proximal to the at least one opening; and a sleeve provided aroundat least a portion of the tube and configured to be translatable along alongitudinal axis of the tube, where a distance from the longitudinalaxis of the tube to an outer edge of the sleeve is at least as large asa distance from the longitudinal axis of the tube to an outer portion ofthe cutting edge. In yet other embodiments, the apparatus includes asubstrate; a plurality of hollow tubes (e.g., needles) affixed to thesubstrate and configured to be at least partially inserted into abiological tissue; at least one opening provided on or in a wall of eachof the hollow tubes; at least one cutting edge protruding from the wallof each of the hollow tubes proximal to the at least one opening; and asleeve provided around at least a portion of each of the tubes, whereeach tube is configured to be translatable along a longitudinal axis ofa corresponding sleeve, and where a distance from the longitudinal axisof each tube to an outer edge of each corresponding sleeve is at leastas large as a distance from the longitudinal axis of the tube to anouter portion of the cutting edge of the tube.

The procedures herein can include one or more optional processes thatpromote effective incision or excision of tissue portions or thatbenefit healing. Such optional processes include cooling, freezing, orpartially freezing the skin portion prior to skin incision or excision(e.g., by applying a cryospray or by contacting a surface of a skinregion with a cooled object for an appropriate duration), where suchcooling and/or freezing can, e.g., increase mechanical stability of thetissue portions; treatment with red or near-infrared light of the skinportion to further promote healing of the tissue; and/or treatment withan optical energy source, such as any described herein (e.g., anablative laser).

Exemplary procedures, methods, and apparatuses are provided in U.S. Pub.Nos. 2012/0041430, 2011/0313429, 2011/0251602, 2012/0226214,2012/0226306 and 2012/0226214; International Pub. Nos. WO 2012/103492,WO 2012/103483, WO 2012/103488, WO 2013/013199, WO 2013/013196, and WO2012/119131; Fernandes et al., “Micro-Mechanical Fractional SkinRejuvenation,” Plastic &Reconstructive Surgery 130(55-1):28 (2012); andFernandes et al., “Micro-Mechanical Fractional Skin Rejuvenation,”Plastic & Reconstructive Surgery 131(2):216-223 (2013), where each ishereby incorporated by reference in its entirety.

Examples Example 1: Method of Treating Skin Regions

A skin region can be treated by any useful method prior to affixing adressing. For example, this method can include forming a plurality ofsmall holes is in the skin through the dermal and epidermal layer.Generally, the dimension of the holes is in the range of 50-500 pm indiameter. Without wishing to be limited by theory, it is envisioned thatup to 40% of the treated skin surface can be removed and that the amountof removed skin determines the extent of the tightening effect. Theholes can be formed surgically, for example, by using a hollow coringneedle (e.g., any described herein). Alternative forms of energy, e.g.,such as laser, non-coherent light, radio-frequency, or ultrasound, canalso be used to form the holes. The holes can be circular or have anyother preferred shape (e.g., an elongated shape). After the formation ofsuch holes, the methods and devices (e.g., dressings) described herein(e.g., in the following Examples) can be employed to reduce skin surfaceand/or tighten skin.

Example 2: Exemplary Tunable Dressing Affixed to the Skin in aTensionless State and then Activated to Compress the Skin (Method 1)

After treating the skin to form a plurality of holes in a skin portion,a tunable dressing can be used to compress the skin. In one embodiment,the dressing comprises an adhesive layer that is in contact with theskin and a tension-regulation layer (a regulatable layer) that isaffixed to the adhesive layer. The tension-regulation layer allowsadjustment of the dimension of the dressing in the plane of the dressing(e.g., parallel to the skin in the x-direction in FIG. 1 or in they-direction (not shown in FIGS. 1A-1D)). Other functional layers includethose providing occlusion to control humidity and/or to promotemoisture-enhanced wound healing, absorption of wound exudate, deliveryof drugs, etc., which can be added to the dressing.

In particular embodiments, the dressing is applied on a treated skinarea in a tensionless state. At that stage, the dressing does not applyany lateral force on the small wounds or holes. The regulatable layer isthen activated, altering the geometry of the dressing. The dressingshrinks and applies a lateral force closing the small wounds.

FIG. 1 describes this exemplary process. Holes, e.g., microscopic holes101, are formed through the dermal and epidermal layer 102 above fattylayer 103 (step A, FIG. 1A). The dressing comprising adhesive 104 andtension-regulation layer 105 is applied on the holes in a tensionlessstate and adheres to the skin surface (step B, FIG. 1B). Thetension-regulation layer 105 of the dressing is activated, altering thedimension of the dressing (shrinking). The shrinking dressing applies alateral compression force 120 on the small holes, and the lateralcompression force closes the holes 101 (step C, FIG. 1C). Any remainingspace in the holes fills with new tissue 106 and completes the healingprocess (step D, FIG. 1D).

The tension-regulation layer can any useful material, e.g., astimulus-responsive polymer, such as a shape-memory material or anydescribed herein. Stimulus-responsive polymers are materials that canchange properties with variation of their environment. For example,geometrical and mechanical properties of certain types of polymers canchange in response to changes in temperature, pH, light, moisture,magnetic field. Shape-memory polymers are stimulus-responsive polymersand exhibit similar behaviors as shape-memory alloys; their dimensionand elastic properties respond to changes in temperature. Fabricsconstituted of shape-memory polymers can be manufactured by knitting andweaving of shape-memory polymer fibers. Exemplary fabrics and polymersare described herein, as well as in Hu et al., “A review ofstimuli-responsive polymers for smart textile applications,” SmartMater. Struct. 21: article 053001 (2012), which is hereby incorporate byreference. In particular embodiments, the regulatable layer includes awoven article having a shape-memory polymer (SMP), which has a firstshape (i.e., before exposure to temperature above the activationthreshold) and a second shape (i.e., after exposure to temperature abovethe activation threshold), and contraction occurs upon exposure to atemperature greater than glass transition temperature of the SMP.Increasing the temperature of the material above a pre-determinedthreshold above body temperature, for example by using a blowgun, canshorten the fibers irreversibly (i.e., by decreasing the temperaturebelow the threshold does not have any impact on the fibers length),therefore contracting the dressing. The SMP composition can be optimizedto have a particular temperature threshold and response to the change intemperature.

Shape-memory materials, e.g., SM Ps, can be programmed with another lowtemperature threshold below room temperature that reverts dimensionalchanges observed after exposure to temperature above the hightemperature threshold. This mechanism allows the user to expand thedressing, for example, if the dressing is too tight afterhigh-temperature contraction. The dressing temperature can be alteredfor example by using a cooling blowgun or by applying a cold surface onthe dressing.

Example 3: Exemplary Tunable Dressing Including a Shape-Memory Alloy(Method 1)

The dressing can include any useful material in the regulatable layer.In one embodiment, the tension-regulation layer can integrate ashape-memory alloy (SMA) material in any useful form, e.g., in the formof wires. The SMA can be geometrically arranged, and its mechanicalproperties can be optimized to respond to particular changes intemperature. In one non-limiting embodiment, a network of SMA wires isarranged in the regulatable layer, e.g., tension-regulation layer 105,e.g., a grid of SMA wires 201, as shown in FIG. 2.

Similar to the dressing in the above-described example, elevation oftemperature can irreversibly alter the wound-dressing geometry, and theSMA can be programmed with another low temperature threshold below roomtemperature that reverts dimensional changes observed after exposure totemperature above the high temperature threshold. In this manner, a usercan expand the dressing, for example, if the dressing is too tight afterhigh-temperature contraction.

The entire dressing or a portion of the dressing (e.g., a limitedsurface of the dressing) can be activated or tuned, such as by heatingthe dressing locally when a thermal-responsive material (e.g., ashape-memory alloy) is used. The level of activation of the dressing canalso be varied by the level of heating, e.g., heating the entirethermally-responsive material or the entire grid including such amaterial will result in full activation, while partial heating willresult in partial activation. In other words, the level of skintightening can be controlled gradually (e.g., in intensity) andspatially (e.g., in the x-, y-, z-, xy-, xz-, yz-, or xyz-direction).

Having described dressing including an SMP and/or SMA in the aboveexamples, the same concept can be applied with one or more otherstimuli, for example, moisture, solvent, pH, light, electric field,and/or magnetic field, by using any useful material (e.g., as describedherein).

Having described exemplary dressing including fibers or grids of an SMPand/or SMA, other form factors can be envisioned for thestimulus-responsive material. Exemplary forms of such materials includea film, a membrane (e.g., as in temperature shrink wrap), or an actuatorhaving more complex geometries.

Example 4: Methods of Tightening of the Skin in a Preferred Direction(Method 2)

The present invention also includes methods of tightening skin in apreferred direction. It might be advantageous to tighten the skin in apre-determined direction, for example, in the case of a breast lift oran eyebrow lift. In one particular example, it is advantageous to closeablations following Langer lines. FIG. 3 shows the skin surface (topview, x-y plane) (in FIG. 3A) before closure of the small holes, (inFIG. 3B) after non-directional tightening, and (in FIG. 3C) afterdirectional tightening along the x-axis. In FIG. 3B, the holes 101 areclosed by pulling tissue from all directions, thereby resulting inpartial hole closure with in holes of smaller diameter. The tighteningeffect is not directional. In FIG. 3C, the holes 101 are closed bypulling tissue along the x-axis, thereby resulting in partial holeclosure with elliptical holes having their long axis along the y-axis.Thus, the tightening effect is unidirectional along the x axis.

The mechanism proposed in Method 1 (Examples 2 and 3) would result innon-directional tightening. The dressing concept can easily be modifiedto provide unidirectional tightening, for example, by aligning theshape-memory polymer fibers along the preferred direction of tightening.Activation of the fibers (i.e., fibers shortening) results in acompression of the dressing along the axis of the fibers. The sameconcept can be applied to shape-memory alloy wires or other actuatorshaving a preferred direction of contraction. FIG. 4A shows an exemplarydressing that integrates a grid of shape-memory alloy wires 201.Contraction of the wires results in non-directional tightening. FIG. 4Bshows the wires aligned in a single-direction arrangement 401.Contraction of the wires results in directional tightening, aligned withthe wires. The contraction of the dressing along the x- and y-axis ofthe dressing shown in FIG. 5 below can be controlled independently. Forexample, a grid of two different stimulus-responsive polymers 501 can beintegrated in the tension-regulation layer 105 (FIG. 5). Polymer fibers502 compressing the dressing along the x-axis responds to a firststimulus (stimulus A), while another type of polymer fibers 503 compressthe dressing along the y-axis and respond to a different stimulus(stimulus B). For example, stimulus A can be thermal (e.g., by using athermal-responsive material, such as any described herein), whilestimulus B is pH (e.g., by using a pH-responsive material, such as anydescribed herein).

An alternative embodiment includes a dressing that expands in adirection perpendicular to the direction of tightening. In FIG. 3, thedressing expands the skin along the y-axis, resulting in closure of theholes along the x-axis. The dressing concept proposed in Method 1(Examples 2 and 3) can be modified by integrating a material thatexpands along an axis in the tension regulation layer (instead ofcontracting). Stimulus-responsive polymers can be programmed to expandwhen exposed to pre-determined stimulus. Actuators expanding along anaxis can also be integrated in the regulatable layer of the dressing.

Example 5: Exemplary Tunable Dressing that Compresses the Skin in aPreferred Compression State (Method 3)

When using dressing to compress the skin and close the holes, it mightbe advantageous to apply an optimal compression level. Tissue can becompressed by a wound dressing as described above in Method 1. The stateof the tissue provides feedback about the optimal compression level. Forexample, it might be advantageous to close the holes but control orregulate the extent of tissue pleating. Tissue pleating might affect thewound healing process. FIG. 6 shows the effect of pleating on holegeometry. Constraints applied on the walls of the holes at the top ofpleats, e.g., hole 601, tend to keep the hole open, therefore increasinghealing time and the risk of scar formation. Constraints applied on thewalls of the hole at the bottom of the pleats, e.g., hole 602, tend toclose the hole. Constraints applied on the walls of the hole on a sideof the pleats, e.g., hole 603, have no effect on the hole. In addition,pleating may prevent conformal adhesion of the wound dressing with thetreated skin, therefore affecting the proper function of the wounddressing that needs to be in contact with the skin. These methods anddevices are applicable not only to compress and expand holes in the skinregion but also to compress and expand slits in the skin region.Pleating can be controlled by inspection of the skin during dressingactivation. Activation can be stopped when the tissue reaches acompression level that starts causing pleating. Alternatively, thedressing can control pleating by having limited flexibility.Accordingly, the methods and devices described herein can be useful forcontrolling pleating (i.e., increasing and/or decreasing the extent ofpleating).

Example 6: Methods Including Elongated Holes to Promote Healing andDirectional Tightening (Method 4)

The present invention also includes optimizing the dimension of theincised or excised tissue portions to promote wound healing. It might beadvantageous to generate small holes that are not circular to promotewound healing. For example, pre-stretching the skin before treatmentwith a circular coring needle generates an elliptical hole in anon-stretched skin. The long axis of the ellipse is perpendicular to thepre-stretching direction. An elliptical hole can generate skintightening preferentially in the direction of the short axis of theellipse. Accordingly, the devices of the invention (e.g., a. dressing,as described herein) can be affixed to a skin portion including one ormore elliptical holes or one or more incised or excised tissue portionshaving one or more elliptical geometries.

Other Embodiments

All publications, patent applications, and patents mentioned in thisspecification are herein incorporated by reference.

Various modifications and variations of the described method and systemof the invention will be apparent to those skilled in the art withoutdeparting from the scope and spirit of the invention. Although theinvention has been described in connection with specific desiredembodiments, it should be understood that the invention as claimedshould not be unduly limited to such specific embodiments. Indeed,various modifications of the described modes for carrying out theinvention that are obvious to those skilled in the fields of medicine,pharmacology, or related fields are intended to be within the scope ofthe invention.

What is claimed is:
 1. A method of skin tightening comprising: (i)producing a plurality of excised tissue portions in a region of skintissue using a system comprising, a plurality of tubes configured tocontact a surface of the skin to generate holes in the skin tissue byexcising portions of the skin tissue; a first actuator configured torotate and/or translate the plurality of tubes relative to the skin; anda suction or pressure system to facilitate removal of tissue portionsfrom the plurality of tubes; and (ii) affixing to the skin region adevice that provides contraction or expansion of said skin region in oneor more directions; wherein at least one of said excised tissue portionshas at least one dimension that is less than 2 mm.
 2. The method ofclaim 1, wherein at least one of said excised tissue portions has alength of more than 1 mm.
 3. The method of claim 1, wherein at least oneof said excised tissue portions has a length of about 3.5 mm.
 4. Themethod of claim 1, wherein an areal fraction of excised tissue portionsis less than about 70% of the skin region.
 5. The method of claim 1,wherein an areal fraction of excised tissue portions is less than about10% of the skin region.
 6. The method of claim 1, wherein said pluralityof excised tissue portions comprise one or more elliptical holes in saidskin region.
 7. The method of claim 1, wherein said affixing step (ii)is performed within about 30 seconds of excising said skin region. 8.The method of claim 1, wherein said affixing step (ii) is performedwithin about ten seconds of excising said skin region.
 9. The method ofclaim 1, wherein said method results in controlling pleating in saidskin region.
 10. The method of claim 1, wherein the device is orcomprises a dressing.
 11. The method of claim 1, wherein the devicecomprises an adhesive material.
 12. The method of claim 1, wherein thedevice comprises an unstretched material.
 13. The method of claim 1,wherein the affixing the device to a skin region provides contraction ofsaid skin region in one direction.
 14. The method of claim 1, whereinthe device comprises one or more shape memory polymer fibers or wires,and wherein contraction of said skin region is provided by aligning theone or more shape memory polymer fibers or wires along one direction.15. The method of claim 1, further comprising increasing a temperatureof the device above a pre-determined threshold above body temperature.16. The method of claim 1, further comprising exposing the device to oneor more stimuli selected from a group consisting of moisture, solvent,pH, light, electric field, and magnetic field.
 17. The method of claim1, further comprising adjusting contraction or expansion of said skinregion to minimize or prevent skin pleating.
 18. The method of claim 1,further comprising pre-stretching the skin region before producing theplurality of excised tissue portions.
 19. The method of claim 1,comprising pre-stretching the skin region before producing the pluralityof excised tissue portions with a circular coring needle to generate anelliptical hole in the skin region when the skin region is notstretched.
 20. The method of claim 1, wherein the skin region is locatedon a face, eyelid, cheek, chin, forehead, lips, nose, neck, chest, arm,leg, and/or a back.
 21. A system for skin tightening comprising: aplurality of tubes configured to contact a surface of the skin togenerate holes in skin tissue by excising portions of the skin tissue; afirst actuator configured to rotate the plurality of tubes relative tothe skin; a suction or pressure system to facilitate removal of skinportions from the tubes; a stop arrangement to control the depth of theexcision and/or the length of the excised tissue portions, wherein thestop arrangement is adjustable along a long axis of at least one of theplurality of tubes to control the depth of excision in the skin; and adevice affixable to a skin region comprising a plurality of the excisedtissue portions, wherein said device provides contraction or expansionof said skin region in one or more directions.
 22. The system of claim21, wherein the first actuator is further configured to translate theplurality of tubes relative to the skin.
 23. The system of claim 21,further comprising a second actuator configured to translate theplurality of tubes relative to the skin.
 24. The system of claim 21,wherein the plurality of tubes comprises between 10 and 20 tubes. 25.The system of claim 21, wherein the plurality of tubes comprises ninetubes.
 26. A method of skin tightening comprising: (i) producing aplurality of excised tissue portions in a region of skin tissue using asystem comprising, a plurality of hollow tubes configured to contact asurface of the skin to generate holes in the skin tissue by excisingportions of the skin tissue, which hollow tubes have an inner diameterthat is less than 0.5 mm; a first actuator configured to rotate and/ortranslate the plurality of tubes relative to the skin; and a suction orpressure system to facilitate removal of tissue portions from theplurality of hollow tubes; and (ii) affixing to the skin region a devicethat provides contraction or expansion of said skin region in one ormore directions.
 27. A method of skin tightening comprising: (i)rotating and/or translating a plurality of tubes relative to a skintissue, and contacting the tubes with a surface of the skin tissue,thereby excising from a region of the skin tissue one or more tissueportions having at least one dimension that is less than 2 mm into thetubes; and applying a suction or pressure force to facilitate removal ofthe excised tissue portions from the tubes; and (ii) affixing a deviceto the region, wherein said device provides contraction or expansion ofsaid region in one or more directions.